HCID 178456583, compound → HCID 178501545, compound

HRID 892122Notes

Reaction equation

[CH2:1]([C@@H:8]1[CH2:19][N:18]2[C:10]([C:11]3[NH:12][C:13]([CH:26]4[CH2:30][CH2:29][CH2:28][CH2:27]4)=[N:14][C:15]=3[N:16]([CH2:21][C:22]([O:24][CH3:25])=[O:23])[C:17]2=[O:20])=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:31]([C@@H]1CN2C(C3NC(C4(O)CCCC4)=NC=3N(CCC)C2=O)=N1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>>[CH2:31]([N:12]1[C:11]2[C:10]3=[N:9][C@H:8]([CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH2:19][N:18]3[C:17](=[O:20])[N:16]([CH2:21][C:22]([O:24][CH3:25])=[O:23])[C:15]=2[N:14]=[C:13]1[CH:26]1[CH2:27][CH2:28][CH2:29][CH2:30]1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.[CH2:1]([C@@H:8]1[CH2:19][N:18]2[C:10]([C:11]3[NH:12][C:13]([CH:26]4[CH2:27][CH2:28][CH2:29][CH2:30]4)=[N:14][C:15]=3[N:16]([CH2:21][C:22]([O:24][CH3:25])=[O:23])[C:17]2=[O:20])=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Reactant 2

HCID 178456583HCID 178456583, compound

HCID 178501545HCID 178501545, compound

Product 2

HCID 69662048HCID 69662048, compound

HCID 178501545HCID 178501545, compoundYield 29%

Procedure

Compound 66 (1.87 g, 4.21 mmol) obtained in Example 66 was dissolved in 1,4-dioxane (30 mL), to the solution was added 2 mol/L aqueous sodium hydroxide (15 mL), and the mixture was stirred with heating at 70° C. for 3 hours. The reaction solution was concentrated under reduced pressure, and then the residue was neutralized by addition of concentrated hydrochloric acid. The deposited crystals were collected by filtration, washed with water and dried to obtain (R)-1,8-dibenzyl-2-cyclopentyl-7,8-dihydro-1H-imidazo[2,1-i]purin-5(4H)-one (Compound 77a, 1.61 g, 90%). Compound 77a (500 mg, 1.08 mmol) was dissolved in N,N-dimethylformamide (5 mL), to the solution were added potassium carbonate (192 mg, 1.41 mmol, 1.2 equivalents) and bromoacetic acid methyl ester (140 μL, 1.41 mmol, 1.2 equivalents), and the mixture was stirred at room temperature for 12 hours. The reaction solution was concentrated under reduced pressure, water was added to the concentrate, the mixture was extracted with chloroform, and the extract was washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=90:10) to obtain (R)-1,8-dibenzyl-2-cyclopentyl-7,8-dihydro-4-methoxycarbonylmethyl-1H-imidazo[2,1-i]purin-5(4H)-one (Compound 77b, 400 mg, 69%). From Compound 77b (850 mg, 1.71 mmol), (R)-8-benzyl-2-cyclopentyl-7,8-dihydro-4-methoxycarbonylmethyl-1H-imidazo[2,1-i]purin-5(4H)-one (Compound 77c, 220 mg, 29%) was obtained in a manner similar to the method by which Compound 40 was obtained from Adduct 40a in Example 40. Compound 77c (200 mg, 0.49 mmol) was dissolved in a mixed solvent of tetrahydrofuran (1 mL) and water (1 mL), to the solution was added lithium hydroxide hydrate (0.04 g, 0.98 mmol), and the mixture was stirred at room temperature for 2.5 hours. The reaction mixture was adjusted to pH 3 with 1 mol/L hydrochloric acid, and the resulting solid was washed with ethanol and collected by filtration to obtain the title compound (180 mg, 93%).

Sources & evidence

ORD record: ord-9f5dbd1b16c645c6b20a1478cbf92918
Source dataset: uspto-grants-2006_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07005430B2

Reaction notes

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