pentyl carbonochloridate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:-2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 35.8 g (0.099 mole) of the compound obtained in Example 2 was mixed with 163 ml of dichloromethane and 11 ml (0.136 mole) of pyridine, and stirred. After cooling the resulting mixture to −5 to 0° C., 15.7 ml (0.109 mole) of n-pentyl chloroformate was added dropwise thereto while maintaining the temperature of the reaction mixture at less than 0° C., followed adding the resulting mixture was warmed to room temperature and stirred for 2 hrs, 1 N HCl thereto. The organic layer was separated, successively washed with 163 ml of saturated sodium bicarbonate and 163 ml of water, dried over anhydrous sodium sulfate, and concentrated under a reduced pressure, to obtain 42.9 g of the title compound. while maintaining the temperature of the reaction mixture at less than 0° C. followed adding the resulting mixture was warmed to room temperature stirred for 2 hrs The organic layer was separated successively washed with 163 ml of saturated sodium bicarbonate and 163 ml of water dried over anhydrous sodium sulfate concentrated under a reduced pressure

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(aminomethyl)-3-methylquinolin-4(1H)-one dihydrochloride (160 mg) in pyridine (8 mL) was added pentyl chloroformate (100 mg), followed by stirring at room temperature for 6 hours. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel chromatography (eluent: chloroform/methanol) to obtain pentyl [(3-methyl-4-oxo-1,4-dihydroquinolin-2-yl)methyl]carbamate (104 mg). The solvent was evaporated under reduced pressure the residue was purified by silica gel chromatography (eluent: chloroform/methanol)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 5′-deoxy-2′,3′-bis-O-(tert-butyldimethylsilyl)-5-iodocytidine (116 mg, 0.200 mmol) in CH2Cl2 (2 ml) pyridine (84 μl, 1.00 mmol), N,N-dimethylamino-pyridine (6 mg, 0.05 mmol), and n-pentyl chloroformate (95 μl, 0.600 mmol) was added at room temperature under Ar. After stirring for 30 minutes, the reaction mixture was partitioned with dichloromethane and water and the organic phase was separated and the water phase was extracted with CH2Cl2 (15 ml×4). The combined organic phase was washed with water and brine, dried over Na2SO4 and filtered. The filtrate was evaporated under reduced pressure. The crude product was purified by flash chromatography on SiO2 (eluent: 20% EtOAc/n-hexane) to give 2′,3′-bis-O-(tert-butyldimethylsilyl)-5′-deoxy-5-iodo-N4-(n-pentyloxycarbonyl)cytidine as a colorless amorphous solid. (132.4 mg, 91% yield). the reaction mixture was partitioned with dichloromethane and water the organic phase was separated the water phase was extracted with CH2Cl2 (15 ml×4) The combined organic phase was washed with water and brine dried over Na2SO4 filtered The filtrate was evaporated under reduced pressure The crude product was purified by flash chromatography on SiO2 (eluent: 20% EtOAc/n-hexane)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 0.976 G. of 4'-cyano-4-hydroxy-biphenyl are dissolved in 10 ml. of absolute pyridine and reacted with 0.90 g. of chloroformic acid n-pentyl ester as in Example 1. The 1.5 g. of yellow, partially crystallized oil obtained according to the procedure described in Example 1 is dissolved in benzene and chromatographed on 90 g. of silica gel. Benzene elutes 1.479 g. of colorless crystrals which are recrystallized from ether-hexane up to constant melting point and clearing point. The pure 4'-cyano-4-biphenylyl n-pentyl carbonate obtained melts at 50.1°-51.0° and has a clearing point of 61.1°. UV (EtOH): ε 270 = 26800. of yellow, partially crystallized oil obtained chromatographed on 90 g of colorless crystrals which are recrystallized from ether-hexane up to constant melting point and clearing point

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-[({[(1-methyl-1H-imidazol-5-yl)(phenyl)methylene]amino}oxy)methyl]pyrimidin-4-amine (200 mg, 0.65 mmol) in 1,4-dioxane (10 mL) were sequentially added triethylamine (0.18 mL, 1.30 mmol) and chloroformic acid pentyl ester (0.38 mL, 2.60 mmol). After stirring at room temperature for 19 h, the mixture was concentrated in vacuo, diluted in ethyl acetate (50 mL), washed with water (20 mL), dried over MgSO4 and concentrated to dryness in vacuo. Purification on silica gel afforded pentyl{2-[({[(1-methyl-1H-imidazol-5-yl)(phenyl)methylene]amino}oxy)methyl]pyrimidin-4-yl}carbamate [26 mg, yield 9%; HPLC/MS: m/z=423 (M+H); log P(HCOOH)=2.66]. the mixture was concentrated in vacuo diluted in ethyl acetate (50 mL) washed with water (20 mL) dried over MgSO4 concentrated to dryness in vacuo Purification on silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-[({[(1-methyl-1H-imidazol-2-yl)(phenyl)methylene]amino}oxy)methyl]pyrimidin-4-amine (200 mg, 0.64 mmol), triethylamine (0.18 mL, 1.29 mmol), chloroformic acid n-amyl ester (0.19 mL, 1.29 mmol) in dichloromethane (10 mL) was stirred 4 h20 at room temperature. After dilution with water (50 mL), the layers were separated and the aqueous layer further extracted with dichloromethane (30 mL). The combined organic layers were dried over MgSO4 and the solvents removed in vacuo. Purification on silica gel afforded pentyl {2-[({[(1-methyl-1H-imidazol-2-yl)(phenyl)methylene]amino}oxy)methyl]pyrimidin-4-yl}carbamate as an oil [34 mg, yield 12%; HPLC/MS: m/z=423 (M+H); log P(HCOOH)=2.28]. After dilution with water (50 mL), the layers were separated the aqueous layer further extracted with dichloromethane (30 mL) The combined organic layers were dried over MgSO4 the solvents removed in vacuo Purification on silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 2-[({[(1-methyl-1H-imidazol-2-yl)(phenyl)methylene]amino}oxy)methyl]pyrimidin-4-amine (200 mg, 0.64 mmol), triethylamine (0.18 mL, 1.29 mmol), chloroformic acid n-amyl ester (0.19 mL, 1.29 mmol) in dichloromethane (10 mL) was stirred 4 h20 at room temperature. After dilution with water (50 mL), the layers were separated and the aqueous layer further extracted with dichloromethane (30 mL). The combined organic layers were dried over MgSO4 and the solvents removed in vacuo. Purification on silica gel afforded pentyl {2-[({[(1-methyl-1H-imidazol-2-yl)(phenyl)methylene]amino}oxy)methyl]pyrimidin-4-yl}carbamate as an oil [34 mg, yield 12%; HPLC/MS: m/z=423 (M+H); log P(HCOOH)=2.28]. After dilution with water (50 mL), the layers were separated the aqueous layer further extracted with dichloromethane (30 mL) The combined organic layers were dried over MgSO4 the solvents removed in vacuo Purification on silica gel

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 4-[({[(4-methyl-1,3-oxazol-5-yl)(phenyl)methylene]amino}oxy)methyl]-1,3-thiazol-2-amine (95 mg, 0.3 mmol) in dichloromethane (2 mL) were added pyridine (36 mg, 0.45 mmol) and after 15 min stirring pentyl carbonochloridoate (91 mg, 0.6 mmol). After stirring at room temperature for 4 h the mixture was passed through a cartridge filled with basic alumina and 1 g silica. After rinsing with dichloromethane the final compound was eluted with heptane/ethylacetate (1/1) to afford after purification on silica pentyl {4-[({[(4-methyl-1,3-oxazol-5-yl)(phenyl)methylene]amino}oxy) methyl]-1,3-thiazol-2-yl}carbamate (60 mg, 44%). filled with basic alumina and 1 g silica After rinsing with dichloromethane the final compound was eluted with heptane/ethylacetate (1/1) to afford after purification on silica pentyl {4-[({[(4-methyl-1,3-oxazol-5-yl)(phenyl)methylene]amino}oxy) methyl]-1,3-thiazol-2-yl}carbamate (60 mg, 44%)