80957-68-2

Basic information

• Product Name: 2-P-TOLYL-4,5,6,7-TETRAHYDRO-OXAZOLO[5,4-C]PYRIDINE
• Synonyms: 5,6,7,8-TETRAHYDRO-[1,6]NAPHTHYRIDINE;1,6-Naphthyridine, 5,6,7,8-tetrahydro-;5,6,7,8-tetrahydro-1,6-naphthyridine(SALTDATA: 2HCl 0.5H2O);5,6,7,8-tetrahydro-1,6-naphthyridine HCl Salt
• CAS NO: 80957-68-2
• Molecular Formula: C₈H₁₀N₂
• Molecular Weight: 134.18
• Product Categories: CHIRAL CHEMICALS;Heterocycle-Pyridine series
• Mol File: 80957-68-2.mol
• Article Data: 10

Chemical Properties

• Boiling Point: 47.62 °C at 760 mmHg
• Flash Point: 103.557 °C
• Appearance: /
• Density: 1.069 g/cm³
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• PKA: 7.95±0.20(Predicted)
• CAS DataBase Reference: 2-P-TOLYL-4,5,6,7-TETRAHYDRO-OXAZOLO[5,4-C]PYRIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 2-P-TOLYL-4,5,6,7-TETRAHYDRO-OXAZOLO[5,4-C]PYRIDINE(80957-68-2)
• EPA Substance Registry System: 2-P-TOLYL-4,5,6,7-TETRAHYDRO-OXAZOLO[5,4-C]PYRIDINE(80957-68-2)

Safety Data

• Hazardous Substances Data: 80957-68-2(Hazardous Substances Data)

Usage

Description

2-P-TOLYL-4,5,6,7-TETRAHYDRO-OXAZOLO[5,4-C]PYRIDINE is a chemical compound that serves as an intermediate in the synthesis of various organic compounds.

Uses

Used in Pharmaceutical Industry:
2-P-TOLYL-4,5,6,7-TETRAHYDRO-OXAZOLO[5,4-C]PYRIDINE is used as a synthetic intermediate for the preparation of quinolizidinone carboxylic acid selective M1 allosteric modulators, which have potential applications in the treatment of neurological disorders and cognitive impairments.

Synthetic route

3-bromo-5,6,7,8-tetrahydro-1,6-naphthyridine (625100-00-7) → 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2)

Conditions	Yield
With palladium 10% on activated carbon; hydrogen In ethanol under 2844.39 Torr; for 3.5h;	100%
With palladium 10% on activated carbon; hydrogen In ethanol under 2844.39 Torr; for 3.5h;	0.5 g

6-benzyl-5,6,7,8-tetrahydro-1,6-naphthyridine (75510-02-0) → 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2)

Conditions	Yield
With hydrogen; palladium on activated charcoal In acetic acid at 50 - 60℃;	94%
With palladium on activated charcoal; hydrogen; acetic acid under 2585.81 Torr; for 48h;	64%
With hydrogen; palladium 10% on activated carbon In acetic acid at 50 - 60℃; under 760.051 Torr; for 2h;	60%
With hydrogen; acetic acid; palladium on activated charcoal at 50 - 60℃; for 2h;

1-phenylmethyl-4-piperidone (3612-20-2) → 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: Et3N; pyridinium acetate / 22 h / 120 °C 2: H2; AcOH / Pd/C / 2 h / 50 - 60 °C View Scheme
Multi-step reaction with 2 steps 1: 37 percent / Et3N, piperidinium acetate / 24 h / 120 °C 2: 94 percent / H2 / Pd-C / acetic acid / 50 - 60 °C View Scheme
Multi-step reaction with 2 steps 1: sodium tetrachloroaurate(III) dihydrate / ethanol / 8 h / 90 °C / Sealed tube 2: palladium on activated charcoal; hydrogen; acetic acid / 48 h / 2585.81 Torr View Scheme

methyl 2-methylnicotinate (65719-09-7) → 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2)

Conditions

Yield

Multi-step reaction with 4 steps 1.1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / tetrachloromethane / 16 h / 90 °C / Inert atmosphere 2.1: tetrabutyl ammonium fluoride / acetonitrile / 16 h / 0 - 30 °C / Inert atmosphere 3.1: hydrogen / methanol; water / 16 h / 50 °C / 2585.81 Torr 4.1: dimethylsulfide borane complex / tetrahydrofuran; dichloromethane / 16 h / 0 - 90 °C 4.2: 0.25 h / 30 °C 4.3: 3 h / 0 - 90 °C View Scheme

methyl 2-(bromomethyl)pyridine-3-carboxylate (116986-08-4) → 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2)

Conditions	Yield
Multi-step reaction with 3 steps 1.1: tetrabutyl ammonium fluoride / acetonitrile / 16 h / 0 - 30 °C / Inert atmosphere 2.1: hydrogen / methanol; water / 16 h / 50 °C / 2585.81 Torr 3.1: dimethylsulfide borane complex / tetrahydrofuran; dichloromethane / 16 h / 0 - 90 °C 3.2: 0.25 h / 30 °C 3.3: 3 h / 0 - 90 °C View Scheme

methyl 2-(cyanomethyl)nicotinate → 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: hydrogen / methanol; water / 16 h / 50 °C / 2585.81 Torr 2.1: dimethylsulfide borane complex / tetrahydrofuran; dichloromethane / 16 h / 0 - 90 °C 2.2: 0.25 h / 30 °C 2.3: 3 h / 0 - 90 °C View Scheme

7,8-Dihydro-1,6-Naphthyridine-5(6H)-one (155058-02-9) → 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2)

Conditions	Yield
Stage #1: 7,8-Dihydro-1,6-Naphthyridine-5(6H)-one With dimethylsulfide borane complex In tetrahydrofuran; dichloromethane at 0 - 90℃; for 16h; Stage #2: In methanol at 30℃; for 0.25h; Stage #3: With hydrogenchloride In 1,4-dioxane at 0 - 90℃; for 3h;

3-bromo-2-picoline (38749-79-0) → 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2)

Conditions

Yield

Multi-step reaction with 5 steps 1.1: triethylamine; [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II) / 16 h / 80 °C / 2585.81 Torr 2.1: N-Bromosuccinimide; 2,2'-azobis(isobutyronitrile) / tetrachloromethane / 16 h / 90 °C / Inert atmosphere 3.1: tetrabutyl ammonium fluoride / acetonitrile / 16 h / 0 - 30 °C / Inert atmosphere 4.1: hydrogen / methanol; water / 16 h / 50 °C / 2585.81 Torr 5.1: dimethylsulfide borane complex / tetrahydrofuran; dichloromethane / 16 h / 0 - 90 °C 5.2: 0.25 h / 30 °C 5.3: 3 h / 0 - 90 °C View Scheme

1-phenylpiperidin-4-one (19125-34-9) → 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrachloroaurate(III) dihydrate / ethanol / Reflux 2: hydrogen; palladium on activated charcoal / acetic acid / 2 h / 60 °C View Scheme

6-phenyl-5,6,7,8-tetrahydro-1,6-naphthyridine → 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2)

Conditions	Yield
With palladium on activated charcoal; hydrogen In acetic acid at 60℃; for 2h;

6-chloro-4-methyl-3-nitro-2-pyrrolidin-1-yl-pyridine (1253378-59-4) + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → 6-(4-methyl-5-nitro-6-pyrrolidin-1-yl-pyridin-2-yl)-5,6,7,8-tetrahydro-[1,6]-naphthyridine (1253378-62-9)

Conditions	Yield
With triethylamine In dimethyl sulfoxide at 110℃; for 8h; Microwave irradiation;	100%

5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → 7,8-dihydro-1,6-naphthyridine (1430218-32-8)

Conditions	Yield
With manganese(IV) oxide In dichloromethane; dimethyl sulfoxide at 20℃; for 24h;	100%

4-((4-(bromomethyl)benzyl)oxy)-2-(2,6-dioxopiperidin-3-yl)isoindoline-1,3-dione (1323408-40-7) + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → 4-((4-((7,8-DIHYDRO-1,6-NAPHTHYRIDIN-6(5H)-YL)METHYL) BENZYL)OXY)-2-(2,6-DIOXOPIPERIDIN-3-YL)ISOINDOLINE-1,3-DIONE (1323403-44-6)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 17h;	99%

2-chloropropionyl chloride (7623-09-8) + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → 6-(2-chloropropionyl)-5,6,7,8-tetrahydro-1,6-naphthyridine (95395-45-2)

Conditions	Yield
With triethylamine In chloroform Ambient temperature;	89%

3-[4-[[4-(bromomethyl)phenyl]methoxy]-1-oxo-isoindolin-2-yl]piperidine-2,6-dione (1323407-86-8) + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → 3-(4-((4-((7,8-DIHYDRO-1,6-NAPHTHYRIDIN-6(5H)-YL)METHYL) BENZYL)OXY)-1-OXOISOINDOLIN-2-YL)PIPERIDINE-2,6-DIONE (1323403-58-2)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In acetonitrile at 20℃; for 1h;	88%

trans-chrotonyl chloride (625-35-4, 3488-22-0, 10487-71-5) + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → 6-crotonoyl-5,6,7,8-tetrahydro-1,6-naphthyridine (95395-49-6)

Conditions	Yield
With pyridine In chloroform 1.) 2 h, 5 deg C; 2.) r.t.;	84%

5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) + 2-bromoethanol (540-51-2) → 6-(2-hydroxyethyl)-5,6,7,8-tetrahydro-1,6-naphthyridine (95395-56-5)

Conditions	Yield
With triethylamine In ethanol for 9.5h; Heating;	69%

1-(2-chloropropionyl)-4-(2-methoxyphenyl)piperazine (95395-48-5) + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → 6-<2-<4-(2-methoxyphenyl)-1-piperazinyl>-1-methyl-2-oxoethyl>-5,6,7,8-tetrahydro-1,6-naphthyridine (95395-47-4)

Conditions	Yield
With triethylamine In ethanol Heating;	60%

5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) + acetyl chloride (75-36-5) → 6-Acetyl-5,6,7,8-tetrahydro-1,6-naphthyridine (90781-15-0)

Conditions	Yield
With triethylamine In dichloromethane	58%

5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) + 1-bromo-3-propanol (627-18-9) → 6-(3-hydroxypropyl)-5,6,7,8-tetrahydro-1,6-naphthyridine (75510-13-3)

Conditions	Yield
With triethylamine In ethanol Heating;	56%

di-tert-butyl dicarbonate (24424-99-5) + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → 7,8-dihydro-5H-[1,6]naphthyridine-6-carboxylic acid tert-butyl ester (259809-44-4)

Conditions	Yield
With sodium hydroxide In water; toluene for 0.333333h;	55%
With sodium hydroxide In toluene for 0.166667h;	981 mg

trimethylsilyl cyanide (7677-24-9) + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → 5,6,7,8-tetrahydro-1,6-naphthyridine-6-nitrile

Conditions	Yield
With potassium fluoride; tetrabutylammomium bromide In acetonitrile at 20℃; for 3h;	47%

2-(5-amino-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)-2-phenylacetic acid + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → 2-(5-amino-2-(furan-2-yl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-7-yl)-1-(7,8-dihydro-1,6-naphthyridin-6 (5H)-yl)-2-phenylethan-1-one

Conditions	Yield
With N-ethyl-N,N-diisopropylamine; HATU In N,N-dimethyl-formamide at 20℃; for 16h;	44%

C16H13ClFN5 + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → C24H22FN7

Conditions	Yield
With N-ethyl-N,N-diisopropylamine at 120℃; Sealed tube;	39%

C17H15ClFN5 + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → C25H24FN7

Conditions	Yield
With N-ethyl-N,N-diisopropylamine Sealed tube;	39%

C16H12ClF2N5 + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → C24H21F2N7

Conditions	Yield
With N-ethyl-N,N-diisopropylamine at 130℃; for 8h;	39%

C16H10ClFN4 + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → C26H21FN6

Conditions	Yield
With N-ethyl-N,N-diisopropylamine at 130℃; for 12h;	38%

5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) + phosphonic acid diethyl ester (762-04-9) → diethyl (5,6,7,8-tetrahydro-1,6-napthyridin-5-yl)phosphonate

Conditions	Yield
With sodium acetate; lithium perchlorate In acetonitrile at 20℃; for 6h; Electrolysis;	38%

C17H14ClFN4 + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → C25H23FN6

Conditions	Yield
With N-ethyl-N,N-diisopropylamine at 120℃; Sealed tube;	35%

1-methyl-6-(3-(oxiran-2-ylmethoxy)phenyl)-1H-benzo[d]imidazole (1616059-77-8) + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → 1-(7,8-dihydro-1,6-naphthyridin-6(5H)-yl)-3-(3-(1-methyl-1H-benzo[d]imidazol-6-yl)phenoxy)propan-2-ol

Conditions	Yield
In ethanol at 80℃; for 5h;	25.4%

N-(2-hydroxy-3-iodopropyl)-2-(quinolin-8-yloxy)acetamide + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → N-[2-hydroxy-3-(5,6,7,8-tetrahydro-1,6-naphthyridin-6-yl)propyl]-2-(quinolin-8-yloxy)acetamide

Conditions	Yield
In methanol at 80℃; for 24h;	19%

tert-butyl cyclopentyl(3-(oxiran-2-ylmethoxy)benzyl)carbamate (1616059-87-0) + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → tert-butyl cyclopentyl(3-(3-(7,8-dihydro-1,6-naphthyridin-6(5H)-yl)-2-hydroxypropoxy)benzyl)carbamate

Conditions	Yield
In ethanol at 100℃; for 0.5h; Microwave irradiation;	8.7%

4-methacryloyl-4-(2-methoxyphenyl)piperazine (96743-74-7) + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → 6-<3-<4-(2-methoxyphenyl)-1-piperazinyl>-2-methyl-3-oxopropyl>-5,6,7,8-tetrahydro-1,6-naphthyridine (95395-52-1)

Conditions	Yield
With N-benzyl-trimethylammonium hydroxide In ethanol Heating;

1-crotonoyl-4-(2-methoxyphenyl)piperazine (95395-50-9) + 5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → 6-<3-<4-(2-methoxyphenyl)-1-piperazinyl>-1-methyl-3-oxopropyl>-5,6,7,8-tetrahydro-1,6-naphthyridine (95395-51-0)

Conditions	Yield
With N-benzyl-trimethylammonium hydroxide In ethanol Heating;

5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → 5,6,7,8-tetrahydro-[1,6]naphthyridine-2-carboxylic acid methyl ester (1057855-79-4)

Conditions	Yield
Multi-step reaction with 4 steps 1: 981 mg / aq. NaOH / toluene / 0.17 h 2: 98 percent / m-chloroperbenzoic acid / CH2Cl2 / 0.5 h / 0 °C 3: 88 percent / N,N-dimethylcarbamyl chloride / CH2Cl2 / 41 h / 20 °C 4: aq. HCl / 3 h / 100 °C View Scheme

5,6,7,8-tetrahydro-1,6-naphthyridine (80957-68-2) → 6-(tert-butoxycarbonyl)-5,6,7,8-tetrahydro-1,6-naphthyridine-1-oxide (259809-45-5)

Conditions	Yield
Multi-step reaction with 2 steps 1: 981 mg / aq. NaOH / toluene / 0.17 h 2: 98 percent / m-chloroperbenzoic acid / CH2Cl2 / 0.5 h / 0 °C View Scheme

Upstream product

• 19125-34-9 1-phenylpiperidin-4-one 
• 155058-02-9 7,8-Dihydro-1,6-Naphthyridine-5(6H)-one 
• 116986-08-4 methyl 2-(bromomethyl)pyridine-3-carboxylate 
• 65719-09-7 methyl 2-methylnicotinate 
• 625100-00-7 3-bromo-5,6,7,8-tetrahydro-1,6-naphthyridine 
• 3612-20-2 1-phenylmethyl-4-piperidone 
• 75510-02-0 6-benzyl-5,6,7,8-tetrahydro-1,6-naphthyridine 
• 38749-79-0 3-bromo-2-picoline 

Downstream Products

• 1036381-91-5 tert‐butyl 2‐oxo‐1,5,7,8‐tetrahydro‐1,6‐naphthyridine‐6(2H)‐carboxylate 
• 1366240-41-6 N-(2-fluoro-4-chlorophenyl)-4-[(7,8-dihydro-1,6-naphthyridin-6(5H)-yl)carbonyl]-( 5-methyl)1,3-thiazol-2-amine 
• 1201844-61-2 N-(2-chloro-5-(7,8-dihydro-1,6-naphthyridin-6(5H)-yl)pyridin-3-yl)-4-fluorobenzenesulfonamide 
• 676994-33-5 2-[4-(3,5-dichloro-phenoxy)-5-methyl-2H-pyrazol-3-yl]-1-(7,8-dihydro-5H-[1,6]naphthyridin-6-yl)-ethanone 
• 95355-91-2 6-<2-<4-(2-butoxyphenyl)-1-piperazinyl>ethyl>-5,6,7,8-tetrahydro-1,6-naphthyridine 
• 95356-01-7 6-<2-<4-(2,5-dimethoxyphenyl)-1-piperazinyl>ethyl>-5,6,7,8-tetrahydro-1,6-naphthyridine 
• 83081-86-1 6-{3-[4-(2-Methoxy-phenyl)-piperazin-1-yl]-butyl}-5,6,7,8-tetrahydro-[1,6]naphthyridine 
• 95355-89-8 6-<2-<4-(2-propoxyphenyl)-1-piperazinyl>ethyl>-5,6,7,8-tetrahydro-1,6-naphthyridine 
• 83081-50-9 6-{3-[4-(2-Methoxy-phenyl)-piperazin-1-yl]-propyl}-5,6,7,8-tetrahydro-[1,6]naphthyridine 
• 95356-04-0 6-{2-[4-(2-Methoxy-phenyl)-piperazin-1-yl]-propyl}-5,6,7,8-tetrahydro-[1,6]naphthyridine 
• 83100-35-0 6-<2-<4-(2-ethoxyphenyl)-1-piperazinyl>ethyl>-5,6,7,8-tetrahydro-1,6-naphthyridine 
• 83081-88-3 6-{3-[4-(2-Methoxy-phenyl)-piperazin-1-yl]-2-methyl-propyl}-5,6,7,8-tetrahydro-[1,6]naphthyridine 
• 83081-63-4 6-{3-[4-(2-Ethoxy-phenyl)-piperazin-1-yl]-propyl}-5,6,7,8-tetrahydro-[1,6]naphthyridine 
• 83081-73-6 6-{2-[4-(2-Methoxy-phenyl)-piperazin-1-yl]-1-methyl-ethyl}-5,6,7,8-tetrahydro-[1,6]naphthyridine 

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