Carbon tetrabromide → HCID 69661588, compound

To Compound 13a (6.65 g, 21.2 mmol) obtained in Example 13 was added (R)-phenylalaminol (4.80 g, 31.7 mmol, 1.5 equivalents) and the mixture was stirred with heating at 150° C. for 4 hours. The reaction mixture was directly purified by silica gel column chromatography (chloroform:methanol=100:1 to 100:3) to obtain an adduct (2.66 g, 30%). To the resulting adduct (2.66 g, 6.37 mmol) was added thionyl chloride (5 mL) and the mixture was stirred with heating at 60° C. for 2.5 hours. After the thionyl chloride was evaporated, the residue was neutralized with saturated aqueous sodium hydrogen carbonate and the mixture was extracted with chloroform. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography (chloroform:methanol=100:1) to obtain (R)-1,8-dibenzyl-7,8-dihydro-4-(n-propyl)-1Himidazo[2,1-i]purin-5(4H)-one (Compound 35a, 1.75 g, 69%). Compound 35a (1.75 g, 4.38 mmol) was dissolved in tetrahydrofuran (30 mL), to the solution was added a 1.54 mol/L solution of lithium diisopropylamide (4.38 mL, 6.75 mmol, 1.5 equivalents) in cyclohexane at −78° C., and the mixture was stirred for 1 hour. To the reaction solution was added a solution (10 mL) of carbon tetrabromide (2.18 g, 6.65 mmol, 1.5 equivalents) in tetrahydrofuran, and the mixture was stirred at −78° C. for 1 hour, then warmed to room temperature and stirred for 2 hours. To the reaction solution was added saturated aqueous ammonium chloride and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography (chloroform:methanol=99.5:0.5), the eluent was concentrated, and to the residue were added acetone and diethyl ether. The deposited crystals were collected by filtration and dried under reduced pressure to obtain the title compound (1.51 g, 72%) as white crystals.

1. stirringthe mixture was stirred at −78° C. for 1 hour
2. stirringstirred for 2 hours
3. extractionthe mixture was extracted with ethyl acetate
4. washThe organic layer was washed with saturated aqueous sodium chloride
5. dry with materialdried over anhydrous sodium sulfate
6. customthe solvent was evaporated
7. customThe residue was purified by silica gel column chromatography (chloroform:methanol=99.5:0.5)
8. concentrationthe eluent was concentrated
9. additionto the residue were added acetone and diethyl ether
10. filtrationThe deposited crystals were collected by filtration
11. customdried under reduced pressure

ORD record

ord-86a5428c0c134013969ba129d75f396e

Source dataset

uspto-grants-2006_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07005430B2