Potassium Carbonate → 8-bromo-7-(4-chlorobenzyl)-1-(2-(1-hydroxycyclopropyl)ethyl)-3-methyl-1H-purine-2,6(3H,7H)-dione

HRID 2200606Notes

Reaction equation

[Br:1][C:2]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]2[C:8](=[O:19])[NH:7][C:6](=[O:20])[N:5]([CH3:21])[C:4]=2[N:3]=1.Br[CH2:23][CH2:24][C:25]1([OH:28])[CH2:27][CH2:26]1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[I-]>[Br:1][C:2]1[N:10]([CH2:11][C:12]2[CH:13]=[CH:14][C:15]([Cl:18])=[CH:16][CH:17]=2)[C:9]2[C:8](=[O:19])[N:7]([CH2:23][CH2:24][C:25]3([OH:28])[CH2:27][CH2:26]3)[C:6](=[O:20])[N:5]([CH3:21])[C:4]=2[N:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 8-bromo-7-(4-chlorobenzyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (150 mg, 0.405 mmol, intermediate 8) in DMF (5 mL) was added 1-(2-bromoethyl)cyclopropanol (94 mg, 0.568 mmol) followed by potassium carbonate (84 mg, 0.609 mmol) and TBAI (catalytic amount). The resulting mixture was stirred at 50° C. overnight. The reaction was diluted with ethyl acetated and washed with brine. The organic phase was dried and concentrated to give crude product which was purified via silica gel chromatography eluting with petroleum ether/ethyl acetate (5:1 to 2:1) to give 8-bromo-7-(4-chlorobenzyl)-1-(2-(1-hydroxycyclopropyl)ethyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (150 mg, 81.6% yield) as light yellow solid. LCMS retention time 1.523 min; LCMS MH+ 455.

Workup

additionThe reaction was diluted with ethyl
washwashed with brine
customThe organic phase was dried
concentrationconcentrated
customto give crude product which
customwas purified via silica gel chromatography
washeluting with petroleum ether/ethyl acetate (5:1 to 2:1)

Sources & evidence

ORD record: ord-a8fad07dc39f436fa4544d4028020f0b
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09359359B2

Reaction notes

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