56610-72-1

Basic information

• Product Name: 7-MAC
• Synonyms: (6R,7S)-Benzhydryl 7-aMino-7-Methoxy-3-(((1-Methyl-1H-tetrazol-5-yl)thio)Methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate;Methoxy Cephalosporins;5-Thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylicacid, 7-aMino-7-Methoxy-3-[[(1-Methyl-1H-tetrazol-5-yl)thio]Methyl]-8-oxo-,diphenylMethyl ester, (6R,7S)-;benzhydryl (6R,7S)-7-amino-7-methoxy-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate;7 beta - amino - 7 alpha - methoxy - 3 - (1 - methyl - 1 h - tetrazolium sulfur - 5 - methyl) - - 5-8 - oxygen generation sulfur - 1 - mixed nitrogen double loop [4.2.0] essien - 2 - methyl - 2 - formic acid diphenyl;7-MAC;7-ACA-3-MTT-7-MO;7-MAC OR 7-AMAC(INTERMEDIATE OF CEFMINOX)
• CAS NO: 56610-72-1
• Molecular Formula: C₂₄H₂₄N₆O₄S₂
• Molecular Weight: 524.61516
• EINECS: 1308068-626-2
• Product Categories: Pharmaceutical raw material;Aromatics;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Sulfur & Selenium Compounds
• Mol File: 56610-72-1.mol

Chemical Properties

• Melting Point: 120°C(lit.)
• Boiling Point: 743.2 °C at 760 mmHg
• Flash Point: 403.2 °C
• Appearance: /
• Density: 1.5 g/cm³
• Vapor Pressure: 5.89E-22mmHg at 25°C
• Refractive Index: 1.733
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: Chloroform (Slightly), Methanol (Slightly, Heated)
• PKA: 3.39±0.60(Predicted)
• CAS DataBase Reference: 7-MAC(CAS DataBase Reference)
• NIST Chemistry Reference: 7-MAC(56610-72-1)
• EPA Substance Registry System: 7-MAC(56610-72-1)

Safety Data

• Hazardous Substances Data: 56610-72-1(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
7-MAC is used as an intermediate in the preparation of Cefmetazole (C242850) and other semi-synthetic antibiotics for the development of new and effective treatments against bacterial infections. Its role in the synthesis process is crucial, as it contributes to the overall effectiveness and potency of the final antibiotic product.

InChI:InChI=1/C24H24N6O4S2/c1-29-23(26-27-28-29)36-14-17-13-35-22-24(25,33-2)21(32)30(22)18(17)20(31)34-19(15-9-5-3-6-10-15)16-11-7-4-8-12-16/h3-12,19,22H,13-14,25H2,1-2H3/t22-,24+/m1/s1

Synthetic route

C31H28N6O5S2 → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
With pyridine; bis(trichloromethyl) carbonate In dichloromethane at -25 - 5℃; for 3h; Reagent/catalyst; Temperature; Solvent; Inert atmosphere;	94.1%

(6R-cis)-7-methoxy-3-<<(1-methyl-1-H-tetrazol-5-yl)thio>methyl>-8-oxo<(phenylacetyl)amino>-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylic acid diphenylmethyl ester (64278-77-9) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
With pyridine; phosphorus pentachloride In methanol; dichloromethane at -30 - 5℃; for 4h; Reagent/catalyst;	91%
Stage #1: (6R-cis)-7-methoxy-3-<<(1-methyl-1-H-tetrazol-5-yl)thio>methyl>-8-oxo<(phenylacetyl)amino>-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylic acid diphenylmethyl ester With pyridine; phosphorus pentachloride In dichloromethane at 5 - 8℃; for 2h; Stage #2: In methanol at -30 - -10℃; for 2h;	90%

2-amino-benzenethiol (137-07-5) + (6R,7S)-7-[1-Chloro-but-(E)-ylideneamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (75072-10-5) → 2-propylbenzo[d]thiazole (17229-76-4) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + (6R,7S)-7-Butyrylamino-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (75072-09-2)

Conditions	Yield
With pyridine In dichloromethane for 1.5h; Ambient temperature;	A 45% B 15% C 23%

(6R,7S)-7-[1-Chloro-but-(E)-ylideneamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (75072-10-5) → 2-propylbenzo[d]thiazole (17229-76-4) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + (6R,7S)-7-Butyrylamino-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (75072-09-2)

Conditions	Yield
With pyridine; 2-amino-benzenethiol In dichloromethane for 1.5h; Ambient temperature;	A 45% B 15% C 23%

2-amino-benzenethiol (137-07-5) + (6R,7S)-7-[5-Benzhydryloxycarbonyl-5-tert-butoxycarbonylamino-1-chloro-pent-(Z)-ylideneamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + 5-Benzothiazol-2-yl-2-tert-butoxycarbonylamino-pentanoic acid benzhydryl ester

Conditions	Yield
With pyridine In dichloromethane Ambient temperature;	A 25% B 35%

(6R,7S)-7-[5-Benzhydryloxycarbonyl-5-tert-butoxycarbonylamino-1-chloro-pent-(Z)-ylideneamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + 5-Benzothiazol-2-yl-2-tert-butoxycarbonylamino-pentanoic acid benzhydryl ester

Conditions	Yield
With pyridine; 2-amino-benzenethiol In dichloromethane Ambient temperature;	A 25% B 35%

(6R)-7t-(3,5-di-tert-butyl-4-hydroxy-benzylideneamino)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (56023-19-9) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
With girard's reagent T In methanol; ethyl acetate Ambient temperature;

(6R,7S)-7-(5-Benzhydryloxycarbonyl-5-tert-butoxycarbonylamino-pentanoylamino)-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (57793-21-2) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: phosgene-pyridine / CH2Cl2 / Ambient temperature 2: 25 percent / pyridine / CH2Cl2 / Ambient temperature View Scheme
Multi-step reaction with 2 steps 1: phosgene-pyridine / CH2Cl2 / Ambient temperature 2: 25 percent / pyridine, o-amino-benzenethiol / CH2Cl2 / Ambient temperature View Scheme

(6R,7S)-7-Butyrylamino-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (75072-09-2) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: phosgene-pyridine / CH2Cl2 / 3 h / Ambient temperature 2: 15 percent / pyridine, o-amino-benzenethiol / CH2Cl2 / 1.5 h / Ambient temperature View Scheme

7β-amino-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>ceph-3-em-4-oic acid benzhydryl ester (53090-86-1) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: (i) benzene, (ii) PbO2, 1,2-dichloroethane, (iii) /BRN= 1098229/, benzene 2: Girard T / ethyl acetate; methanol / Ambient temperature View Scheme

7-Aminocephalosporanic acid (957-68-6) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 7 steps 1.1: boron trifluoride diethyl etherate / acetonitrile / 2.5 h / 50 °C 2.1: sodium hydrogencarbonate / water; acetone / 3.67 h / 0 - 20 °C 3.1: dicyclohexyl-carbodiimide; dmap / dichloromethane / -20 °C 4.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 °C 5.1: phosphorus trichloride / dichloromethane / 3 h / Reflux 6.1: tert-butylhypochlorite / tetrahydrofuran; methanol / 0.37 h / -78 °C / Inert atmosphere 7.1: pyridine; phosphorus pentachloride / dichloromethane / 2 h / 5 - 8 °C 7.2: 2 h / -30 - -10 °C View Scheme
Multi-step reaction with 7 steps 1: boron trifluoride diethyl etherate / acetonitrile / 2.5 h / 50 °C 2: sodium hydrogencarbonate / acetone; water / 3 h / 0 - 25 °C 3: dicyclohexyl-carbodiimide; dmap / dichloromethane / -20 °C 4: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 - 5 °C 5: phosphorus trichloride / dichloromethane / 3 h / Reflux 6: tert-butylhypochlorite; lithium methanolate / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 7: pyridine; phosphorus pentachloride / dichloromethane; methanol / 4 h / -30 - 5 °C View Scheme

(6R,7R)-7-amino-3-[(1H-1-methyltetrazol-5-yl)thio]methylceph-3-em-4-carboxylic acid (24209-38-9) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 6 steps 1.1: sodium hydrogencarbonate / water; acetone / 3.67 h / 0 - 20 °C 2.1: dicyclohexyl-carbodiimide; dmap / dichloromethane / -20 °C 3.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 °C 4.1: phosphorus trichloride / dichloromethane / 3 h / Reflux 5.1: tert-butylhypochlorite / tetrahydrofuran; methanol / 0.37 h / -78 °C / Inert atmosphere 6.1: pyridine; phosphorus pentachloride / dichloromethane / 2 h / 5 - 8 °C 6.2: 2 h / -30 - -10 °C View Scheme
Multi-step reaction with 6 steps 1: sodium hydrogencarbonate / acetone; water / 3 h / 0 - 25 °C 2: dicyclohexyl-carbodiimide; dmap / dichloromethane / -20 °C 3: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 - 5 °C 4: phosphorus trichloride / dichloromethane / 3 h / Reflux 5: tert-butylhypochlorite; lithium methanolate / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 6: pyridine; phosphorus pentachloride / dichloromethane; methanol / 4 h / -30 - 5 °C View Scheme

(6R,7R)-3-((1-methyl-1H-tetrazol-5-ylthio)methyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-aza-bicyclo [4.2.0]oct-2-ene-2-carboxylic acid (47653-82-7) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 5 steps 1.1: dicyclohexyl-carbodiimide; dmap / dichloromethane / -20 °C 2.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 °C 3.1: phosphorus trichloride / dichloromethane / 3 h / Reflux 4.1: tert-butylhypochlorite / tetrahydrofuran; methanol / 0.37 h / -78 °C / Inert atmosphere 5.1: pyridine; phosphorus pentachloride / dichloromethane / 2 h / 5 - 8 °C 5.2: 2 h / -30 - -10 °C View Scheme
Multi-step reaction with 5 steps 1: dicyclohexyl-carbodiimide; dmap / dichloromethane / -20 °C 2: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 - 5 °C 3: phosphorus trichloride / dichloromethane / 3 h / Reflux 4: tert-butylhypochlorite; lithium methanolate / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 5: pyridine; phosphorus pentachloride / dichloromethane; methanol / 4 h / -30 - 5 °C View Scheme

(6R,7R)-benzhydryl-3-((1-methyl-1H-tetrazol-5-ylthio)methyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-azabicyclo[4.2.0]oct-3-ene-2-carboxylic → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 °C 2.1: phosphorus trichloride / dichloromethane / 3 h / Reflux 3.1: tert-butylhypochlorite / tetrahydrofuran; methanol / 0.37 h / -78 °C / Inert atmosphere 4.1: pyridine; phosphorus pentachloride / dichloromethane / 2 h / 5 - 8 °C 4.2: 2 h / -30 - -10 °C View Scheme
Multi-step reaction with 4 steps 1: 3-chloro-benzenecarboperoxoic acid / chloroform / 6 h / 0 - 5 °C 2: phosphorus trichloride / dichloromethane / 3 h / Reflux 3: tert-butylhypochlorite; lithium methanolate / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 4: pyridine; phosphorus pentachloride / dichloromethane; methanol / 4 h / -30 - 5 °C View Scheme

C31H28N6O5S2 (68474-81-7) → diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: phosphorus trichloride / dichloromethane / 3 h / Reflux 2.1: tert-butylhypochlorite / tetrahydrofuran; methanol / 0.37 h / -78 °C / Inert atmosphere 3.1: pyridine; phosphorus pentachloride / dichloromethane / 2 h / 5 - 8 °C 3.2: 2 h / -30 - -10 °C View Scheme
Multi-step reaction with 3 steps 1: phosphorus trichloride / dichloromethane / 3 h / Reflux 2: tert-butylhypochlorite; lithium methanolate / tetrahydrofuran / 0.33 h / -78 °C / Inert atmosphere 3: pyridine; phosphorus pentachloride / dichloromethane; methanol / 4 h / -30 - 5 °C View Scheme

diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + Glyoxilic acid (298-12-4) → C26H24N6O6S2

Conditions	Yield
Stage #1: Glyoxilic acid With 1,1'-carbonyldiimidazole In dichloromethane Stage #2: diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate In dichloromethane at 40℃; for 10h; Reagent/catalyst;	98.8%

2,2-dimercaptoacetic acid + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → C26H26N6O5S4

Conditions	Yield
With 1,1'-carbonyldiimidazole In ethyl acetate at 40℃; for 10h;	98.6%

chlorocarbonyl-[4-(4-methoxy-benzyloxy)-phenyl]-acetic acid 4-methoxy-benzyl ester (64952-86-9) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R,7S)-7-Methoxy-7-{2-(4-methoxy-benzyloxycarbonyl)-2-[4-(4-methoxy-benzyloxy)-phenyl]-acetylamino}-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (66216-32-8)

Conditions	Yield
With pyridine	75%

2-[(3S)-(4-ethyl-2,3-dioxo-1-piperazinyl)carboxamido]-3-formyloxybutyryl chloride + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R,7S)-7-[[(3S)-2-[(4-ethyl-2,3-dioxo-1-piperazinyl)carboxamido]-3-formyloxy-1-oxobutyl]amino]-7-methoxy-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid diphenylmethyl ester

Conditions	Yield
With triethylamine In dichloromethane at -10℃;	51.5%

gloutaric dichloride (2873-74-7) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → C29H30N6O7S2

Conditions	Yield
With pyridine In dichloromethane Cooling with ice;	17%

L-α-[[[(4-methoxyphenyl)-methoxy]carbonyl]amino]-2-thiopheneacetic acid (59966-06-2) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-7t-[(Ξ)-2-(4-methoxy-benzyloxycarbonylamino)-2-thiophen-2-yl-acetylamino]-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (64044-40-2)

Conditions	Yield
(i) diisopropylethylamine, isobutyl chloroformate, CH2Cl2, (ii) /BRN= 5406406/; Multistep reaction;

cyanomethylmercapto acetyl chloride (52069-55-3) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → Cefmetazole (56796-20-4, 82263-66-9)

Conditions	Yield
(i) PhNEt2, 1,2-dichloroethane, (ii) CF3CO2H, anisole; Multistep reaction;

(1-methyl-4-nitro-1H-imidazol-2-ylsulfanyl)-acetyl chloride + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-7t-[2-(1-methyl-4-nitro-1H-imidazol-2-ylsulfanyl)-acetylamino]-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (72193-33-0)

Conditions	Yield
(i) PhNEt2, 1,2-dichloro-ethane, (ii) CF3CO2H, anisole; Multistep reaction;

(3-methyl-5-nitro-3H-imidazol-4-ylsulfanyl)-acetyl chloride (72193-39-6) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-7t-[2-(3-methyl-5-nitro-3H-imidazol-4-ylsulfanyl)-acetylamino]-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (72193-31-8)

Conditions	Yield
(i) PhNEt2, 1,2-dichloro-ethane, (ii) CF3CO2H, anisole; Multistep reaction;

(1-methyl-5-nitro-1H-imidazol-2-ylsulfanyl)-acetyl chloride + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-7t-[2-(1-methyl-5-nitro-1H-imidazol-2-ylsulfanyl)-acetylamino]-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (72193-34-1)

Conditions	Yield
(i) PhNEt2, 1,2-dichloro-ethane, (ii) CF3CO2H, anisole; Multistep reaction;

(1-methyl-5-nitro-1H-imidazol-4-ylsulfanyl)-acetyl chloride + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-7t-[2-(1-methyl-5-nitro-1H-imidazol-4-ylsulfanyl)-acetylamino]-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (72193-32-9)

Conditions	Yield
(i) PhNEt2, 1,2-dichloro-ethane, (ii) CF3CO2H, anisole; Multistep reaction;

(R)-2-amino-4-thiophen-2-yl-4H-oxazol-5-one; hydrochloride (67645-41-4) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7t-((R)-2-thiophen-2-yl-2-ureido-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (67780-07-8)

Conditions	Yield
With methyloxirane In dichloromethane; N,N-dimethyl-formamide

(S)-2-amino-4-thiophen-2-yl-4H-oxazol-5-one; hydrochloride (67645-39-0) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7t-((S)-2-thiophen-2-yl-2-ureido-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (65642-60-6)

Conditions	Yield
With methyloxirane In dichloromethane; N,N-dimethyl-formamide

diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + Carbonic acid benzyl ester 4-chlorocarbonylmethyl-phenyl ester (86862-84-2) → (6R,7S)-7-[2-(4-Benzyloxycarbonyloxy-phenyl)-acetylamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester (86862-87-5)

Conditions	Yield
With pyridine In dichloromethane at 0℃; for 0.5h; Yield given;

diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R,7R)-7-[2-Carboxy-2-(4-hydroxy-phenyl)-acetylamino]-6-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Conditions	Yield
Multi-step reaction with 2 steps 1: 75 percent / pyridine 2: 100 percent / AlCl3, anisole / 0.5 h / 0 °C View Scheme

diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7t-((Ξ)-2-amino-2-thiophen-3-yl-acetylamino)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid

Conditions	Yield
Multi-step reaction with 2 steps 1: (i) diisopropylethylamine, isobutyl chloroformate, CH2Cl2, (ii) /BRN= 5406406/ 2: CF3CO2H, anisole View Scheme

diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7t-((S)-2-thiophen-2-yl-2-ureido-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (65700-47-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: propyleneoxide / CH2Cl2; dimethylformamide 2: CF3CO2H, anisole / CH2Cl2 View Scheme

diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) → (6R)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7t-((R)-2-thiophen-2-yl-2-ureido-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid (74378-97-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: propyleneoxide / CH2Cl2; dimethylformamide 2: CF3CO2H, anisole / CH2Cl2 View Scheme

diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + 2-Bromoacetyl bromide (598-21-0) → 7-bromoacetamide-7-methoxy-3-(1-methyl-1H-5-tetrazolyl)thiomethyl-3-cephem-4-carboxylic acid diphenyl methyl ester (70035-75-5)

Conditions	Yield
Stage #1: diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate; 2-Bromoacetyl bromide With pyridine In dichloromethane at -30 - -20℃; for 1h; Stage #2: With N-Bromosuccinimide In methanol; dichloromethane at 0 - 5℃; for 1h;
With N,N-dimethyl-aniline In ethyl acetate at -5 - 0℃;

methanol (67-56-1) + (6R-cis)-7-amino-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-7-(methylthio)-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylic acid diphenylmethyl ester (67366-04-5) + diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate (56610-72-1) + 2-Bromoacetyl bromide (598-21-0) → 7-bromoacetamide-7-methoxy-3-(1-methyl-1H-5-tetrazolyl)thiomethyl-3-cephem-4-carboxylic acid diphenyl methyl ester (70035-75-5)

Conditions

Yield

Stage #1: (6R-cis)-7-amino-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-7-(methylthio)-8-oxo-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylic acid diphenylmethyl ester; diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>-Δ3-cephem-4-carboxylate; 2-Bromoacetyl bromide With pyridine In dichloromethane at -30 - -20℃; for 1h; Stage #2: In dichloromethane; water at 0 - 5℃; Stage #3: methanol With N-Bromosuccinimide; sodium thiosulfate Purification / work up; more than 3 stages;

Upstream product

• 137-07-5 2-amino-benzenethiol 
• 75072-10-5 (6R,7S)-7-[1-Chloro-but-(E)-ylideneamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 64278-77-9 (6R-cis)-7-methoxy-3-<<(1-methyl-1-H-tetrazol-5-yl)thio>methyl>-8-oxo<(phenylacetyl)amino>-5-thia-1-azabicyclo<4.2.0>oct-2-ene-2-carboxylic acid diphenylmethyl ester 
• 68474-81-7 C₃₁H₂₈N₆O₅S₂ 
• 47653-82-7 (6R,7R)-3-((1-methyl-1H-tetrazol-5-ylthio)methyl)-8-oxo-7-(2-phenylacetamido)-5-thia-1-aza-bicyclo [4.2.0]oct-2-ene-2-carboxylic acid 
• 24209-38-9 (6R,7R)-7-amino-3-[(1H-1-methyltetrazol-5-yl)thio]methylceph-3-em-4-carboxylic acid 
• 957-68-6 7-Aminocephalosporanic acid 
• 53090-86-1 7β-amino-3-<<(1-methyl-1H-tetrazol-5-yl)thio>methyl>ceph-3-em-4-oic acid benzhydryl ester 
• 75072-09-2 (6R,7S)-7-Butyrylamino-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 57793-21-2 (6R,7S)-7-(5-Benzhydryloxycarbonyl-5-tert-butoxycarbonylamino-pentanoylamino)-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 56023-19-9 (6R)-7t-(3,5-di-tert-butyl-4-hydroxy-benzylideneamino)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 83934-73-0 (R)-3-(1-Methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7-[2,2,3-trichloro-3-phenyl-prop-(E)-ylideneamino]-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 53090-86-1 (R)-7-Amino-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 83934-79-6 (S)-7-[(Z)-2-Chloro-3-phenyl-prop-2-en-(E)-ylideneamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 

Downstream Products

• 56796-20-4 Cefmetazole 
• 66216-32-8 (6R,7S)-7-Methoxy-7-{2-(4-methoxy-benzyloxycarbonyl)-2-[4-(4-methoxy-benzyloxy)-phenyl]-acetylamino}-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 61807-78-1 7β-bromoacetamido-7α-methoxy-3-(1-methyltetrazol-5-yl)thiomethyl-Δ³-cephem-4-carboxylic acid 
• 74356-00-6 cefotetan disodium 
• 69712-56-7 cefotetan 
• 70035-75-5 7-bromoacetamide-7-methoxy-3-(1-methyl-1H-5-tetrazolyl)thiomethyl-3-cephem-4-carboxylic acid diphenyl methyl ester 
• 65700-47-2 (6R)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7t-((S)-2-thiophen-2-yl-2-ureido-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid 
• 86862-87-5 (6R,7S)-7-[2-(4-Benzyloxycarbonyloxy-phenyl)-acetylamino]-7-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 65642-60-6 (6R)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7t-((S)-2-thiophen-2-yl-2-ureido-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 67780-07-8 (6R)-7c-methoxy-3-(1-methyl-1H-tetrazol-5-ylsulfanylmethyl)-8-oxo-7t-((R)-2-thiophen-2-yl-2-ureido-acetylamino)-(6rH)-5-thia-1-aza-bicyclo[4.2.0]oct-2-ene-2-carboxylic acid benzhydryl ester 
• 77119-51-8 7β-<(R)-2-<3-(3,4-diacetoxybenzoyl)-3-methylureido>-2-phenylacetamido>-7α-methoxy-3-<(1-methyl-1H-tetrazol-5-yl)thiomethyl>-3-cephem-4-carboxylic acid 
• 77127-99-2 7β-<(R)-2-<3-(3,4-dihydroxybenzoyl)-3-methylureido>-2-phenylacetamido>-7α-methoxy-3-<(1-methyl-1H-tetrazol-5-yl)thiomethyl>-3-cephem-4-carboxylic acid 

Relevant articles and documents

7 β-amino -7 α-methoxy-3-cephem compound preparation method

The invention relates to a preparation method of a medical raw material 7beta-amino-7lapha-methoxy-3-cephem compound. Methods in prior arts have the problems of more steps and low yield. According to the 7beta-amino-7lapha-methoxy-3-cephem compound preparation method provided by the invention, a beta-lactam compound is adopted as a raw material, and is subjected to a reaction with bis(trichloromethyl)carbonate under the existence of an organic alkali, such that a iminochloride-beta-lactam compound is produced; methanol is added for alcoholysis, such that the 7beta-amino-7lapha-methoxy-3-cephem compound is produced. The method provided by the invention has the advantages of mild and easy-to-control reaction conditions, high yield, no product of 7alpha-methoxy-7beta-amino-3-cephem compound isomer, and easy separation. With the method, the 7beta-amino-7lapha-methoxy-3-cephem compound product with ultrahigh purity can be obtained.

A novel synthetic route to 7-MAC from 7-ACA

An efficient and practical seven-step procedure is described for the synthesis of (6R,7S)-benzhydryl-7-amino-7-methoxy-3-((1-methyl-1H-tetrazol-5-ylthio)methyl)-8-oxo-5-thia-1-aza-bicyclo [4.2.0]oct-2-ene-2-carboxylate (7-MAC, 3) with overall yield of 49?%. This synthesis features a convenient and highly selective method for the introduction of 7α-methoxy group to cephalosporin nucleus in 10 using MeOLi/t-BuOCl in THF.

Synthesis method of methoxy cephalosporin drug intermediate 7-MAC

The invention provides a synthesis method of a methoxy cephalosporin drug intermediate 7alpha-methoxy-7beta-amino-3-(1-methyl-1H-tetrazole-5-methylthio)-3-cephem-4-diphenylmethyl carboxylate (7-MAC). The synthesis method comprises steps as follows: 7-aminocephalosporanic acid (7-ACA) is taken as a raw material, a side chain at a C-3 site and amino at a C-7beta site are modified firstly, oxidative rearrangement and reduction are performed after protection of diphenylmethyl at a C-4 site, a methoxy group is selectively introduced to a C-7alpha site, an amino protecting group is removed finally, and 7-MAC is obtained through 7-step reaction. According to the synthesis method of the methoxy cephalosporin drug intermediate 7-MAC, the defects that byproducts such as methyl mercaptan and the like are required to be removed while the methoxy group is introduced in the existing synthesis technology are overcome. Meanwhile, the synthesis method of the methoxy cephalosporin drug intermediate7-MAC does not adopt diazo compounds, and accordingly, danger such as explosion possibly caused by the diazo compounds is eliminated.

Deacylation of Amides: Removal of the Acyl Side-chain from Cephamycin Derivatives

Diphenylmethyl (6R,7S)-7-amino-7-methoxy-3-methyl>-Δ3-cephem-4-carboxylate (9) is obtained from a cephamycin C derivative by treatment of an imino chloride intermediate with o-aminobenzenethiol.

3-Heterothiomethyl-7α-methoxy-7β-tetrazolylmethylthioacetamido-3-cephem derivatives

7α-Methoxy-7β-tetrazolylmethylthioacetamido-3-cephem derivatives which have a heterothiomethyl substituent in the 3-position are novel compounds which are useful as antimicrobial agents.

A new semisynthetic 7α methoxycephalosporin, CS-1170: 7β [[(cyanomethyl)thio]acetamido] 7α methoxy 3 [[(1 methyl 1H tetrazol 5 yl)thio]methyl] 3 cephem 4 carboxylic acid

The synthesis and antimicrobial activity of a new semisynthetic 7α methoxycephalosporin, 7β [[(cyanomethyl)thio]acetamido] 7α methoxy [[(1 methyl 1H tetrazol 5 yl)thio] methyl] 3 cephem 4 carboxylic acid (CS 1170), are described. This compound shows interesting antibacterial activity when compared to cefoxitin and cephalothin.