Water → HCID 69661400, compound

6-Methylthio-3-(n-propyl)-7H-purin-2(3H)-one (Compound B8, 11.8 g, 52.5 mmol), which was obtained by the method described in Journal of Heterocyclic Chemistry (J. Heterocycl. Chem.), 30, p. 241, 1993, was dissolved in N,N-dimethylformamide (200 mL). To the solution was added sodium hydride (1.51 g, 63.0 mmol, 1.2 equivalents) and the mixture was stirred at room temperature for 30 minutes. To the reaction solution was added chloromethyl methyl ether (4.85 mL, 63.9 mmol, 1.2 equivalents) and the mixture was stirred at room temperature for 1 hour. To the reaction solution was added saturated aqueous ammonium chloride, the mixture was extracted with chloroform, and the organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate. Then, the solvent was evaporated, and to the resulting residue was added diethyl ether. The deposited crystals were collected by filtration to obtain a methoxymethyl adduct. (R)-8-Benzyl-2-bromo-7,8-dihydro-1-methoxymethyl-4-(n-propyl)-1H-imidazo[2,1-i]purin-5(4H)-one (Compound 36a, 2.81 g, 6.52 mmol), which was obtained from the methoxymethyl adduct in a manner similar to that in Example 35, was dissolved in N,N-dimethylformamide (26 mL), to the solution was added an about 15% aqueous solution of methylmercaptan sodium salt (6.10 mL, 13.1 mmol, 2.0 equivalents), and the mixture was stirred at room temperature for three days. To the reaction solution was added water, the mixture was extracted with chloroform, then the organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, and the solvent was evaporated. The reaction residue was purified by silica gel column chromatography (chloroform:methanol=98:2) and the eluent was concentrated. To the residue was added acetonitrile, and the deposited crystals were collected by filtration to obtain the title compound (2.17 g, 84%) as white crystals.

1. extractionthe mixture was extracted with chloroform
2. washthe organic layer was washed with saturated aqueous sodium chloride
3. dry with materialdried over anhydrous sodium sulfate
4. customthe solvent was evaporated
5. customThe reaction residue was purified by silica gel column chromatography (chloroform:methanol=98:2)
6. concentrationthe eluent was concentrated
7. additionTo the residue was added acetonitrile
8. filtrationthe deposited crystals were collected by filtration

ORD record

ord-9c2d75b5a06f466f98e98fb5640363bd

Source dataset

uspto-grants-2006_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07005430B2