Potassium Carbonate → 8-chloro-7-(4-chlorobenzyl)-3-ethyl-1-(3-hydroxypropyl)-1H-purine-2,6(3H,7H)-dione

HRID 2200637Notes

Reaction equation

[Cl:1][C:2]1[NH:10][C:9]2[C:8](=[O:11])[N:7]([CH2:12][CH2:13][CH2:14][OH:15])[C:6](=[O:16])[N:5]([CH2:17][CH3:18])[C:4]=2[N:3]=1.Br[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[I-]>[Cl:1][C:2]1[N:10]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)[C:9]2[C:8](=[O:11])[N:7]([CH2:12][CH2:13][CH2:14][OH:15])[C:6](=[O:16])[N:5]([CH2:17][CH3:18])[C:4]=2[N:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 8-chloro-3-ethyl-1-(3-hydroxypropyl)-1H-purine-2,6(3H,7H)-dione (2.2 g, 8.09 mmol) in DMF (10 mL) was added 1-(bromomethyl)-4-chlorobenzene (2.47 g, 12.11 mmol), followed by potassium carbonate (2.23 g, 16.18 mmol) and TBAI (15 mg, 0.042 mmol). The reaction was stirred at 50° C. for 2 h. The reaction was cooled to room temperature and partitioned between ethyl acetate and water. The organic phase was washed with brine and dried over sodium sulfate, and concentrated to give a crude product which was purified by silica gel chromatography eluting with petroleum/ethyl acetate (5:1 to 1:2) to give 8-chloro-7-(4-chlorobenzyl)-3-ethyl-1-(3-hydroxypropyl)-1H-purine-2,6(3H,7H)-dione (2.3 g, 71.8% yield) as white solid. LCMS retention time 1.485 min; LCMS MH+ 397.

Workup

temperatureThe reaction was cooled to room temperature
custompartitioned between ethyl acetate and water
washThe organic phase was washed with brine
dry with materialdried over sodium sulfate
concentrationconcentrated
customto give a crude product which
customwas purified by silica gel chromatography
washeluting with petroleum/ethyl acetate (5:1 to 1:2)

Sources & evidence

ORD record: ord-4e676740e42e4d85bc6aa7901b69966b
Source dataset: uspto-grants-2016_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09359359B2

Reaction notes

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