261909-49-3

Basic information

• Product Name: L-Alanine, N-(chlorophenoxyphosphinyl)-, 1-Methylethyl ester
• Synonyms: L-Alanine, N-(chlorophenoxyphosphinyl)-, 1-Methylethyl ester;N-(Chlorophenoxyphosphinyl)-L-alanine 1-methylethyl ester;isopropyl(chloro(phenoxy)phosphoryl)-L-alaninate;phenyl(isopropoxy-L-alaninyl) phosphorochloridate;EOS-60850
• CAS NO: 261909-49-3
• Molecular Formula: C₁₂H₁₇ClNO₄P
• Molecular Weight: 305.694441
• EINECS: -0
• Mol File: 261909-49-3.mol
• Article Data: 68

Chemical Properties

• Boiling Point: 376.5±44.0 °C(Predicted)
• Appearance: white powder
• Density: 1.249±0.06 g/cm3 (20 oC 760 Torr)
• PKA: -6.04±0.70(Predicted)
• CAS DataBase Reference: L-Alanine, N-(chlorophenoxyphosphinyl)-, 1-Methylethyl ester(CAS DataBase Reference)
• NIST Chemistry Reference: L-Alanine, N-(chlorophenoxyphosphinyl)-, 1-Methylethyl ester(261909-49-3)
• EPA Substance Registry System: L-Alanine, N-(chlorophenoxyphosphinyl)-, 1-Methylethyl ester(261909-49-3)

Safety Data

• Hazardous Substances Data: 261909-49-3(Hazardous Substances Data)

Usage

Description

L-Alanine, N-(chlorophenoxyphosphinyl)-, 1-methylethyl ester is a chemical compound derived from L-alanine, a non-essential amino acid. It features a chlorophenoxyphosphinyl group and an isopropyl ester group, which contribute to its unique chemical properties. L-Alanine, N-(chlorophenoxyphosphinyl)-, 1-methylethyl ester may be utilized in various applications, including organic synthesis and as a reagent in chemical reactions. Additionally, it holds potential for the development of pharmaceuticals and other bioactive compounds. Due to its nature, it is crucial to handle and use this compound with care, adhering to proper safety protocols and handling procedures.

Uses

Used in Organic Synthesis:
L-Alanine, N-(chlorophenoxyphosphinyl)-, 1-methylethyl ester is used as a reagent in organic synthesis for its unique chemical properties, enabling the creation of various complex organic compounds.
Used in Pharmaceutical Development:
L-Alanine, N-(chlorophenoxyphosphinyl)-, 1-methylethyl ester is used as a precursor in the development of pharmaceuticals, potentially contributing to the creation of new drugs and therapeutic agents.
Used in Bioactive Compounds Research:
L-Alanine, N-(chlorophenoxyphosphinyl)-, 1-methylethyl ester is utilized in research for the development of bioactive compounds, which may have applications in medicine, agriculture, and other fields.
Used in Chemical Reactions:
As a reagent, L-Alanine, N-(chlorophenoxyphosphinyl)-, 1-methylethyl ester is employed in various chemical reactions to facilitate specific transformations or syntheses, contributing to the advancement of chemical research and technology.
Used in Research and Development:
In the research and development industry, L-Alanine, N-(chlorophenoxyphosphinyl)-, 1-methylethyl ester is used as a key component in the exploration of new chemical entities and their potential applications in various fields, including but not limited to medicine, biotechnology, and materials science.

Synthetic route

O-phenyl phosphorodichloridate (770-12-7) + alanine isopropyl ester hydrochloride (39613-92-8, 62062-56-0, 62062-65-1) → phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3)

Conditions	Yield
With triethylamine In tert-butyl methyl ether at -65 - -50℃; for 2h; Inert atmosphere; Cooling with acetone-dry ice;	100%
With triethylamine In tert-butyl methyl ether at -55℃; for 2h;	100%
With triethylamine In dichloromethane at -78 - 20℃; for 2.5h; Inert atmosphere;	93%

isopropyl L-alanine (39825-33-7) + O-phenyl phosphorodichloridate (770-12-7) → phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3)

Conditions	Yield
With triethylamine In dichloromethane at -78 - 20℃; for 1.25h; Inert atmosphere;	99%
With triethylamine In dichloromethane	78%
With N-ethyl-N,N-diisopropylamine In dichloromethane at -80℃; for 2h;

O-phenyl phosphorodichloridate (770-12-7) + (isopropoxy-2-oxo-ethyl-L-alaninyl)ammonium salt → phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3)

Conditions	Yield
With triethylamine In dichloromethane at -78 - 20℃; Inert atmosphere;	80%

toluene-4-sulfonic acid; compound with 2-amino-propionic acid isopropyl ester + O-phenyl phosphorodichloridate (770-12-7) → phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3)

Conditions	Yield
With triethylamine In dichloromethane at -78 - 20℃;	55%
With triethylamine In dichloromethane at -78 - 20℃;

toluene-4-sulfonic acid (104-15-4) → phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: toluene / Heating 2: triethylamine / CH2Cl2 / -78 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: toluene / 24 h / 120 °C 2: triethylamine / dichloromethane / -78 - 20 °C View Scheme

phenol (108-95-2) → phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3)

Conditions	Yield
Multi-step reaction with 2 steps 1: trichlorophosphate; triethylamine / dichloromethane / 2 h / -78 - 20 °C 2: triethylamine / dichloromethane / 2 h / -78 - 20 °C View Scheme
Multi-step reaction with 2 steps 1: trichlorophosphate; triethylamine / dichloromethane / -78 - 20 °C 2: triethylamine / dichloromethane / 2 h / -78 °C View Scheme
Multi-step reaction with 2 steps 1: triethylamine; trichlorophosphate / dichloromethane / 2 h / -78 - 20 °C 2: triethylamine / dichloromethane / 2 h / -78 - 20 °C View Scheme

C6H12ClNO2 + O-phenyl phosphorodichloridate (770-12-7) → phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3)

Conditions	Yield
With triethylamine In dichloromethane at -78 - 20℃;	760 g

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + 2,3,4,5,6-pentafluorophenol (771-61-9) → (S)-2-[(2,3,4,5,6-pentafluorophenoxy)phenoxyphosphorylamino]propionic acid isopropyl ester (1256490-52-4)

Conditions	Yield
With triethylamine In dichloromethane at 0 - 25℃; for 1h; Inert atmosphere;	100%
With triethylamine In dichloromethane at -5 - 20℃; for 20.33h; Inert atmosphere;	41%
With triethylamine In dichloromethane at 0 - 20℃; Inert atmosphere;

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + 1-[(2R,3R,4R,5R)-4-(benzyloxy)-3-fluoro-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione → (2S)-isopropyl 2-{[({(2R,3R,4R,5R)-3-(benzyloxy)-5-[2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl]-4-fluoro-4-methyltetrahydrofuran-2-yl}methoxy)(phenoxy)phosphoryl]amino}propanoate

Conditions	Yield
Stage #1: 1-[(2R,3R,4R,5R)-4-(benzyloxy)-3-fluoro-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl]pyrimidine-2,4(1H,3H)-dione With isopropylmagnesium chloride, lithium chloride complex In tetrahydrofuran at -20℃; for 2h; Stage #2: phenyl(isopropoxy-L-alaninyl) phosphorochloridate In tetrahydrofuran at -20℃; for 4h;	99%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + C22H41FN2O6Si2 → C34H57FN3O10PSi2

Conditions	Yield
Stage #1: C22H41FN2O6Si2 With isopropylmagnesium chloride In tetrahydrofuran at -25℃; for 2h; Stage #2: phenyl(isopropoxy-L-alaninyl) phosphorochloridate In tetrahydrofuran at -25 - -5℃; for 15h; Temperature;	99%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + 1-((3aR,4R,6S,6aS)-6-fluoro-6-(hydroxymethyl)-2-methoxy-3a-methyltetrahydrofuro [3,4-d][1,3]dioxol-4-yl)pyrimidine-2,4-(1H,3H)-dione (1613589-05-1) → C24H31FN3O11P

Conditions	Yield
Stage #1: 1-((3aR,4R,6S,6aS)-6-fluoro-6-(hydroxymethyl)-2-methoxy-3a-methyltetrahydrofuro [3,4-d][1,3]dioxol-4-yl)pyrimidine-2,4-(1H,3H)-dione With isopropylmagnesium chloride In tetrahydrofuran at 0℃; for 0.333333h; Stage #2: phenyl(isopropoxy-L-alaninyl) phosphorochloridate In tetrahydrofuran at 20℃;	93%
Stage #1: 1-((3aR,4R,6S,6aS)-6-fluoro-6-(hydroxymethyl)-2-methoxy-3a-methyltetrahydrofuro [3,4-d][1,3]dioxol-4-yl)pyrimidine-2,4-(1H,3H)-dione With isopropylmagnesium chloride In tetrahydrofuran at 0℃; for 0.333333h; Stage #2: phenyl(isopropoxy-L-alaninyl) phosphorochloridate In tetrahydrofuran at 0 - 20℃;	93%
Stage #1: 1-((3aR,4R,6S,6aS)-6-fluoro-6-(hydroxymethyl)-2-methoxy-3a-methyltetrahydrofuro [3,4-d][1,3]dioxol-4-yl)pyrimidine-2,4-(1H,3H)-dione With isopropylmagnesium chloride In tetrahydrofuran at 0℃; for 0.333333h; Stage #2: phenyl(isopropoxy-L-alaninyl) phosphorochloridate In tetrahydrofuran at 20℃;	93%
Stage #1: 1-((3aR,4R,6S,6aS)-6-fluoro-6-(hydroxymethyl)-2-methoxy-3a-methyltetrahydrofuro [3,4-d][1,3]dioxol-4-yl)pyrimidine-2,4-(1H,3H)-dione With isopropylmagnesium chloride In tetrahydrofuran at 0℃; for 0.333333h; Stage #2: phenyl(isopropoxy-L-alaninyl) phosphorochloridate In tetrahydrofuran at 20℃;	93%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + O2',O3'-isopropylidene-1-methyl-guanosine (23392-07-6) → C26H35N6O9P

Conditions	Yield
With 1-methyl-1H-imidazole In tetrahydrofuran; acetonitrile at 20℃; for 3h;	91%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + (2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4-chloro-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-yl tert-butyl carbonate → isopropyl ((((2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-3-((tert-butoxycarbonyl)oxy)-4-chloro-4-fluorotetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate

Conditions	Yield
With tert-butylmagnesium chloride In tetrahydrofuran at 20℃; for 1h;	89%
Stage #1: (2R,3R,4R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4-chloro-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-yl tert-butyl carbonate With tert-butylmagnesium chloride In tetrahydrofuran at 0℃; for 0.333333h; Stage #2: phenyl(isopropoxy-L-alaninyl) phosphorochloridate In tetrahydrofuran at 20℃; for 1h;	89%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + 5(R)-<5-methyl-2,4(1H,3H)-pyrimidinedione>tetrahydro-3(S)-furanmethanol (146558-01-2) → 1'-(thymin-1-yl)-2',3'-dideoxy-β-D-apio-D-furanose [phenyl-(isopropoxy-L-alaninyl)]phosphate (1610460-03-1)

Conditions	Yield
With 1-methyl-1H-imidazole In tetrahydrofuran at 25℃; for 48h; Inert atmosphere;	88%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + 2',3'-O-cyclopentylidene-4'-azidoinosine (926309-62-8) → C27H33N8O9P (1170666-22-4)

Conditions	Yield
With tert-butylmagnesium bromide In tetrahydrofuran at 20℃; for 17h;	87%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + 1-((1R,3S,5S)-3-(hydroxymethyl)-2-oxabicyclo[3.1.0]hexan-1-yl)pyrimidine-2,4(1H,3H)-dione → isopropyl((((1R,3S,5S)-1-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2-oxabicyclo[3.1.0]hexan-3-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate

Conditions	Yield
Stage #1: 1-((1R,3S,5S)-3-(hydroxymethyl)-2-oxabicyclo[3.1.0]hexan-1-yl)pyrimidine-2,4(1H,3H)-dione With tert-butylmagnesium chloride In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: phenyl(isopropoxy-L-alaninyl) phosphorochloridate In tetrahydrofuran for 2h; Inert atmosphere;	85%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + (2R,3R,5R)-5-(4-amino-2-oxopyrimidin-1(2H)-yl)-4,4-difluoro-2-(hydroxymethyl)tetrahydrofuran-3-yl tert-butyl carbonate (250698-51-2) → 2′-deoxy-2′,2′-difluoro-3′-O-(tert-butoxycarbonyloxy)-D-cytidine-5′-O-[phenyl(isopropoxy-L-alaninyl)]phosphate

Conditions	Yield
With tert-butylmagnesium chloride In tetrahydrofuran at 20℃; for 16h; Inert atmosphere;	84%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + diethyl (2-amino-9-((2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)-9H-purin-6-yl)phosphonate (1345969-94-9) → isopropyl ((((2R,3R,4R,5R)-5-(2-amino-6-(diethoxyphosphoryl)-9H-purin-9-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate

Conditions	Yield
With 1-methyl-1H-imidazole In tetrahydrofuran; acetonitrile at 20℃; for 3h;	77%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + 4-amino-1-((1R,3S,5S)-3-(hydroxymethyl)-2-oxabicyclo[3.1.0]hexan-1-yl)pyrimidin-2(1H)-one → C22H29N4O7P

Conditions	Yield
Stage #1: 4-amino-1-((1R,3S,5S)-3-(hydroxymethyl)-2-oxabicyclo[3.1.0]hexan-1-yl)pyrimidin-2(1H)-one With tert-butylmagnesium chloride In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Stage #2: phenyl(isopropoxy-L-alaninyl) phosphorochloridate In tetrahydrofuran Inert atmosphere;	72%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + (3S,4R,5S,6R)-3-acetamido-6-(hydroxymethyl)-tetrahydro-2H-pyran-2,4,5-triyl triacetate (63597-75-1) → (3S,4R,5S,6R)-3-acetamido-6-((((((S)-1-isopropoxy-1-oxopropan-2-yl)amino)(phenoxy)phosphoryl)oxy)methyl)tetrahydro-2H-pyran-2,4,5-triyl triacetate

Conditions	Yield
Stage #1: (3S,4R,5S,6R)-3-acetamido-6-(hydroxymethyl)-tetrahydro-2H-pyran-2,4,5-triyl triacetate With tert-butylmagnesium chloride In tetrahydrofuran at 0℃; for 0.5h; Inert atmosphere; Stage #2: phenyl(isopropoxy-L-alaninyl) phosphorochloridate In tetrahydrofuran at 0 - 20℃; for 12h; Inert atmosphere;	68%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + C21H34N2O5Si → isopropyl ((((3aS,4R,6R,6aR)-4-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-2,2-dimethyl-tetrahydrospiro[cyclopenta[d][1,3] dioxole-5,1’-cyclopropan]-6-yl)methoxy)(phenoxy)phos phoryl)-L-alaninate

Conditions	Yield
With 1-methyl-1H-imidazole In tetrahydrofuran at -78 - 20℃; Inert atmosphere;	68%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + sodium pentafluorophenolate (2263-53-8) → (S)-2-[((S)-(2,3,4,5,6-pentafluorophenoxy)(phenoxy)phosphoryl)amino]propionic acid isopropyl ester (1334513-02-8)

Conditions	Yield
Stage #1: phenyl(isopropoxy-L-alaninyl) phosphorochloridate; sodium pentafluorophenolate In tetrahydrofuran at -10℃; Stage #2: With triethylamine In n-heptane; tert-butyl methyl ether pH=8;	66.81%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + 4-((benzyloxy)amino)-1-((2R,3R,4R,5R)-3,4-dihydroxy-5-(hydroxymethyl)-3-methyltetrahydrofuran-2-yl)pyrimidin-2(1H)-one (1609192-93-9) → (2S)-isopropyl 2-(((((2R,3R,4R,5R)-5-(4-((benzyloxy)amino)-2-oxopyrimidin-1(2H)-yl)-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoate (1609193-17-0)

Conditions	Yield
With 1-methyl-1H-imidazole In tetrahydrofuran at 20℃; for 3h; Inert atmosphere;	66%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + 2',3'-O,O-cyclopentylidene-4'-azidouridine (926309-54-8) → 2-propyl N-[{1-[(3aR,4R,6R,6aS)-4-azido-tetrahydro-4-(hydroxymethyl)-2,2-cyclopentylfuro[3,4-d][1,3]dioxol-6-yl]pyrimidine-2,4(1H,3H)-dione} (phenoxy)-phosphoryl]-L-alaninate

Conditions	Yield
Stage #1: 2',3'-O,O-cyclopentylidene-4'-azidouridine With tert-butylmagnesium chloride In tetrahydrofuran for 0.25h; Stage #2: phenyl(isopropoxy-L-alaninyl) phosphorochloridate In tetrahydrofuran for 17h; Further stages.;	64%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + (+)-9-[(1′R,2′R,3′R,4′R)-2′-fluoro-3′-hydroxy-4′-(hydroxymethyl)-5′-methylenecyclopentan-1′-yl]-adenine (1307273-70-6) → {[(1R,3R,4R)-3-(6-amino-9H-purin-9-yl)-4-fluoro-5-hydroxy-2-methylenecyclopentyl]methoxy}(phenoxyphosphoryl amino) propionic Acid Isopropyl Ester

Conditions	Yield
With 1-methyl-1H-imidazole In tetrahydrofuran at 0 - 20℃; Inert atmosphere;	61%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + 5'-(5-hexadecyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)phospho-AZT → 5'-(phosphoamidate-phospho)-AZT

Conditions	Yield
With triethylamine In 1,4-dioxane; acetonitrile for 18h;	60%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + 5-(6-amino-9H-purin-9-yl)-2,2,3,3,4,4-hexafluoropentan-1-ol → isopropyl (((5-(6-amino-9H-purin-9-yl)-2,2,3,3,4,4-hexafluoropentyl)oxy)(phenoxy)phosphoryl)-L-alaninate

Conditions	Yield
Stage #1: 5-(6-amino-9H-purin-9-yl)-2,2,3,3,4,4-hexafluoropentan-1-ol With 1-methyl-1H-imidazole In tetrahydrofuran at 0℃; for 0.25h; Stage #2: phenyl(isopropoxy-L-alaninyl) phosphorochloridate In tetrahydrofuran at 20℃; for 2h;	60%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + N'-(9-((2-hydroxyethoxy)-methyl)-6-oxo-6,9-dihydro-1H-purin-2-yl)-N,N-dimethylformimidamide (100699-59-0) → C23H32N7O7P (1184942-68-4)

Conditions	Yield
With tert-butylmagnesium chloride In tetrahydrofuran at 20℃; Inert atmosphere;	59%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + 1′-cyano-2′-C-methyl-4-aza-7,9-dideazaadenosine (1191237-49-6) → (2S)-isopropyl 2-((((2R,3R,4R,5R)-5-(4-aminopyrrolo[1,2-f]-[1,2,4]triazin-7-yl)-5-cyano-3,4-dihydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphorylamino)propanoate (1350735-57-7)

Conditions	Yield
With 1-methyl-1H-imidazole; trimethyl phosphite In tetrahydrofuran at 0 - 20℃; for 1.5h;	59%
With 1-methyl-1H-imidazole; trimethyl phosphite In tetrahydrofuran at 0 - 20℃; for 1.5h;	59%
With 1-methyl-1H-imidazole; trimethyl phosphite In tetrahydrofuran at 0 - 25℃; for 1.5h;	59%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + C11H13N5O7 → C23H29N6O11P

Conditions	Yield
Stage #1: C11H13N5O7 With tert-butylmagnesium bromide In tetrahydrofuran at 0 - 20℃; for 0.5h; Inert atmosphere; Stage #2: phenyl(isopropoxy-L-alaninyl) phosphorochloridate In tetrahydrofuran at 0 - 20℃; for 20h; Inert atmosphere;	58%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + (3aR,4R,6S,6aS)-4-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-6-fluoro-6-(hydroxymethyl)-2-methoxytetrahydrofuro[3,4-d][1,3]dioxole-4-carbonitrile → isopropyl((((3aS,4S,6R,6aR)-6-(4-aminopyrrolo[2,1-f][1,2,4]triazin-7-yl)-6-cyano-4-fluoro-2-methoxytetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methoxy)(phenoxy)phosphoryl)-L-alaninate

Conditions	Yield
With 1-methyl-1H-imidazole In acetonitrile at 0 - 20℃; for 1h; Inert atmosphere;	57%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + C22H26N8O3 → propan-2-yl (2S)-2-([phenoxy[(2R)-2-[3-[6-([[4-(piperidine-1-carbonyl)pyridin-2-yl]carbamoyl]amino)pyridin-2-yl]-4H-1,2,4-triazol-4-yl]propoxy]phosphoryl]amino)propanoate

Conditions	Yield
With tert-butylmagnesium chloride In N,N-dimethyl-formamide at -40 - 20℃; for 16h; Inert atmosphere;	56%

phenyl(isopropoxy-L-alaninyl) phosphorochloridate (261909-49-3) + 4-((2-hydroxyethoxy)methyl)-3-oxo-3,4-dihydropyrazine-2-carboxamide → isopropyl ((2-((3-carbamoyl-2-oxopyrazin-1(2H)-yl)methoxy)ethoxy)(phenoxy)phosphoryl)-L-alaninate

Conditions	Yield
Stage #1: 4-((2-hydroxyethoxy)methyl)-3-oxo-3,4-dihydropyrazine-2-carboxamide With pyridine; 1-methyl-1H-imidazole In tetrahydrofuran at 20℃; for 0.333333h; Inert atmosphere; Stage #2: phenyl(isopropoxy-L-alaninyl) phosphorochloridate In tetrahydrofuran at 20℃; Inert atmosphere;	55%

Upstream product

• 770-12-7 O-phenyl phosphorodichloridate 
• 39613-92-8 alanine isopropyl ester hydrochloride 
• 108-95-2 phenol 
• 39825-33-7 isopropyl L-alanine 
• 104-15-4 toluene-4-sulfonic acid 

Downstream Products

• 1184942-68-4 C₂₃H₃₂N₇O₇P 
• 1442452-48-3 (2S)-isopropyl 2-(((((2R,3S,4R,5R)-4-((tert-butoxycarbonyl)amino)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)-phosphoryl)amino)propanoate 
• 1285658-68-5 4'-azido-2'-deoxy-2'-methylarabinouridine-5'-(O-phenyl-N-(S)-1-(isopropoxycarbonyl)ethyl)phosphoramidate 
• 1496552-16-9 sofosbuvir 

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Synthesis of 1-((4 R,5S,6R,7R)-5,6-dihydroxy-7-(hydroxymethyl)spiro[2.4]heptan-4-yl)pyrimidine-2,4(1H,3H)-dione (12) and its phosphoramidate prodrug 18 is reported. The synthesis of the targeted compound 12 was initiated from triol 1. By the introduction of a substituent methylene group at 6-position of 4, followed by Simmons-Smith cyclopropanation and amination, key intermediate 10 was synthesized. The intermediate amine 10 was utilized to synthesize the nucleoside 12. Furthermore, the nucleoside 12 was derivatized to 2′-α-hydroxy-2′-β-methyl (23) and 2′-α-fluoro-2′-β-methyl (27) analogs. All synthesized derivatives of spiro-cyclopropyl carbocyclic uridine analogs 12, 18, 23 and 27 were evaluated for anti-HCV activity, but none of the compounds, reported in this article show any anti-HCV activity.

Synthesis of an Anti-hepatitis B Agent, 2′-Fluoro-6′-methylene-carbocyclic Adenosine (FMCA) and Its Phosphoramidate (FMCAP)

2′-Fluoro-6′-methylene-carbocyclic adenosine (FMCA, 12) and its phosphoramidate prodrug (FMCAP, 14) have been proven as a potential anti-HBV agent against both adefovir-resistant as well as lamivudine-resistant double (rtL180M/rtM204V) mutants. Furthermore, in vitro, these agents have demonstrated significant activity against lamivudine/entecavir triple mutants (L180M + S202G + M204V). These preliminary results encourage us for further biological evaluation of FMCA and FMCAP to develop as a potential clinical candidate as an anti-HBV agent, which may overcome the problem of drug resistance in HBV therapy. To support the preclinical exploration, a scalable synthesis of this molecule was needed. In this communication, a practical and scalable synthesis of FMCA, and its prodrug, is reported via ketone 1. The selective opening of the isopropylidene group of 2 led to compound 3. Protection of the allylic hydroxyl group of 3, followed by fluorination and deprotection, afforded the key intermediate 10, which was condensed with a Boc-protected adenine, followed by deprotection, furnished the target nucleoside FMCA (12) in high yield. Further coupling of phosphorochloridate of L-alanine isopropyl ester (13) with FMCA gave its phosphoramidate prodrug FMCAP (14) in good yield.

Prodrug compound and application ofprodrug compound in treatment of cancer

The present invention provides a compound indicated by a formula (I), pharmaceutically acceptable salts or esters thereof, a pharmaceutical composition of the compound, and application of the compoundand the pharmaceutical composition in the inhibition or regulation of the activity of tyrosine kinase and treating disease symptoms or symptoms including cancer mediated by tyrosine kinase.

Compound for treating viral infection and preparation method and application of compound

The invention provides a preparation for treating viral infection and pneumovirus subfamily viral infection, a method, a compound as shown in a formula (I) and a method and intermediate for synthesis of the compound as shown in the formula (I).