Products Categories
CAS No.: | 764659-72-5 |
---|---|
Name: | (2R,5S)-5-(4-amino-5-fluoro-2-oxo-1(2H)-pyrimidinyl)-1,3-Oxathiolane-2-carboxylic acid, (1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl ester |
Article Data: | 14 |
Molecular Structure: | |
Formula: | C18H26FN3O4S |
Molecular Weight: | 399.487 |
Synonyms: | (2R,5S)-5-(4-Amino-5-fluoro-2-oxo-1(2H)-pyrimidinyl)-1,3-oxathiolane-2-carboxylic acid (1R,2S,5R)-5-methyl-2-(1-methylethyl)cyclohexyl ester; emtricitabine intermediate FCME |
EINECS: | 1592732-453-0 |
Density: | 1.47 |
Boiling Point: | 508.5±60.0 °C(Predicted) |
PSA: | 122.73000 |
LogP: | 2.89910 |
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5S)-5-(4-amino-5-fluoro-2-oxo-1,2-dihydro-1-pyrimidinyl)-1,3-oxathialane-2-carboxylate
Conditions | Yield |
---|---|
With hydrogenchloride In dichloromethane; water at 20 - 25℃; | 96.7% |
Flucytosine
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5R)-5-(methylcarbonyloxy)-1,3-oxathiolane-2-carboxylate
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5S)-5-(4-amino-5-fluoro-2-oxo-1,2-dihydro-1-pyrimidinyl)-1,3-oxathialane-2-carboxylate
Conditions | Yield |
---|---|
Stage #1: (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5R)-5-(methylcarbonyloxy)-1,3-oxathiolane-2-carboxylate With triethylsilane; iodine In dichloromethane at 0℃; for 1h; Inert atmosphere; Stage #2: Flucytosine With N,O-bis-(trimethylsilyl)-acetamide In dichloromethane at 0 - 20℃; for 1h; Reagent/catalyst; Inert atmosphere; stereoselective reaction; | 91% |
Stage #1: Flucytosine With chloro-trimethyl-silane; 1,1,1,3,3,3-hexamethyl-disilazane at 25 - 130℃; Inert atmosphere; Stage #2: (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5R)-5-(methylcarbonyloxy)-1,3-oxathiolane-2-carboxylate With zirconium(IV) chloride In dichloromethane at 25 - 30℃; for 6h; Inert atmosphere; | 80% |
2-trimethylsilyloxy-4-trimethylsilylamino-5-fluoropyrimidine
5S-chloro-[1,3]oxathiolane-2R-carboxilic acid 2-(1'R,2'S,5'R)-isopropyl-5-methyl-cyclohexyl ester
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5S)-5-(4-amino-5-fluoro-2-oxo-1,2-dihydro-1-pyrimidinyl)-1,3-oxathialane-2-carboxylate
Conditions | Yield |
---|---|
Stage #1: 2-trimethylsilyloxy-4-trimethylsilylamino-5-fluoropyrimidine; 5S-chloro-[1,3]oxathiolane-2R-carboxilic acid 2-(1'R,2'S,5'R)-isopropyl-5-methyl-cyclohexyl ester With triethylamine In dichloromethane at 42 - 45℃; for 19h; Heating / reflux; Stage #2: With water at 25℃; for 0.5h; | 81% |
Flucytosine
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5S)-5-(4-amino-5-fluoro-2-oxo-1,2-dihydro-1-pyrimidinyl)-1,3-oxathialane-2-carboxylate
Conditions | Yield |
---|---|
Stage #1: 5R-hydroxy-[1,3]oxathiolane-2R-carboxylic acid 2-(1'R,2'S,5'R)-isopropyl-5-methyl-cyclohexyl ester With thionyl chloride In dichloromethane at 0 - 15℃; for 2h; Stage #2: Flucytosine With ammonium sulfate; 1,1,1,3,3,3-hexamethyl-disilazane In toluene Reflux; Stage #3: With triethylamine at 90℃; Reflux; | 50.5% |
Stage #1: 5R-hydroxy-[1,3]oxathiolane-2R-carboxylic acid 2-(1'R,2'S,5'R)-isopropyl-5-methyl-cyclohexyl ester With thionyl chloride In dichloromethane; toluene; N,N-dimethyl-d6-formamide at 10 - 15℃; for 2h; Stage #2: Flucytosine With ammonium sulfate; 1,1,1,3,3,3-hexamethyl-disilazane In dichloromethane; N,N-dimethyl-formamide; toluene Reflux; Further stages; | 50.5% |
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5S)-5-(4-amino-5-fluoro-2-oxo-1,2-dihydro-1-pyrimidinyl)-1,3-oxathialane-2-carboxylate
Conditions | Yield |
---|---|
Stage #1: Flucytosine With methanesulfonic acid; 1,1,1,3,3,3-hexamethyl-disilazane In toluene for 3h; Stage #2: 5-chloro-[1,3]oxathiolane-2-carboxylic acid 2-isopropyl-5-methyl-cyclohexyl ester With triethylamine In dichloromethane at 20 - 25℃; for 20 - 21h; Heating / reflux; | |
Multi-step reaction with 4 steps 1.1: triethylamine / dichloromethane / 8 - 50 °C 2.1: toluene / 1 h / Molecular sieve 3.1: toluene / 75 - 80 °C 4.1: methanesulfonic acid / methanol / 4 h 4.2: 0.17 h View Scheme |
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5S)-5-(methylcarbonyloxy)-1,3-oxathiolane-2-carboxylate
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5S)-5-(4-amino-5-fluoro-2-oxo-1,2-dihydro-1-pyrimidinyl)-1,3-oxathialane-2-carboxylate
Conditions | Yield |
---|---|
Stage #1: Flucytosine With methanesulfonic acid; 1,1,1,3,3,3-hexamethyl-disilazane In toluene for 3h; Heating / reflux; Stage #2: (1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5S)-5-(methylcarbonyloxy)-1,3-oxathiolane-2-carboxylate With trimethylsilyl iodide In dichloromethane at 20℃; for 2h; |
Flucytosine
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5S)-5-(4-amino-5-fluoro-2-oxo-1,2-dihydro-1-pyrimidinyl)-1,3-oxathialane-2-carboxylate
Conditions | Yield |
---|---|
Stage #1: (2R,5R)-5-hydroxy-[1,3]-oxathiolane-2-carboxylic acid, 2S-isopropyl-5R-methyl-1R-cyclohexyl ester With thionyl chloride; methanesulfonic acid; N,N-dimethyl-formamide In dichloromethane at 8 - 20℃; for 8h; Heating / reflux; Stage #2: Flucytosine With 1,1,1,3,3,3-hexamethyl-disilazane In dichloromethane; toluene for 5h; Heating / reflux; Stage #3: With triethylamine In dichloromethane; water; toluene at 25 - 65℃; for 6h; pH=7.8; Heating / reflux; |
(2R,5R)-5-hydroxy-1,3-oxathiolane-2-carboxylic acid (1R,2S,5R)-5-methyl-2-isopropylcyclohexyl ester
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5S)-5-(4-amino-5-fluoro-2-oxo-1,2-dihydro-1-pyrimidinyl)-1,3-oxathialane-2-carboxylate
Conditions | Yield |
---|---|
Multi-step reaction with 3 steps 1.1: pyridine / dmap / di-isopropyl ether / 5 - 20 °C 2.1: 1,1,1,3,3,3-hexamethyl-disilazane / methanesulfonic acid / toluene / 6 h / Reflux 2.2: 10 - 55 °C 3.1: methanesulfonic acid / di-isopropyl ether; methanol / 0.83 h / 20 °C 3.2: 1 h / 20 °C View Scheme |
(1'R,2'S,5'R)-menthyl-5(R,S)-acetoxy-[1,3]-oxathiolane-2R-carboxylate
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5S)-5-(4-amino-5-fluoro-2-oxo-1,2-dihydro-1-pyrimidinyl)-1,3-oxathialane-2-carboxylate
Conditions | Yield |
---|---|
Multi-step reaction with 2 steps 1.1: 1,1,1,3,3,3-hexamethyl-disilazane / methanesulfonic acid / toluene / 6 h / Reflux 1.2: 10 - 55 °C 2.1: methanesulfonic acid / di-isopropyl ether; methanol / 0.83 h / 20 °C 2.2: 1 h / 20 °C View Scheme |
(1R,2S,5R)-2-isopropyl-5-methylcyclohexyl (2R,5S)-5-(4-amino-5-fluoro-2-oxo-1,2-dihydro-1-pyrimidinyl)-1,3-oxathialane-2-carboxylate
Conditions | Yield |
---|---|
Stage #1: C21H30FN3O5S With methanesulfonic acid In methanol; di-isopropyl ether at 20℃; for 0.833333h; Stage #2: With triethylamine In hexane; water; ethyl acetate at 20℃; for 1h; |