Dimethylformamide → 2-chloro-9-(cyclopropylmethyl)-6-morpholin-4-yl-9H-purine

HRID 1876490Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].[CH:7]1([CH2:10]Br)[CH2:9][CH2:8]1.CN(C)C=O.[Cl:17][C:18]1[N:26]=[C:25]2[C:21]([N:22]=[CH:23][NH:24]2)=[C:20]([N:27]2[CH2:32][CH2:31][O:30][CH2:29][CH2:28]2)[N:19]=1>C(OCC)(=O)C>[Cl:17][C:18]1[N:26]=[C:25]2[C:21]([N:22]=[CH:23][N:24]2[CH2:10][CH:7]2[CH2:9][CH2:8]2)=[C:20]([N:27]2[CH2:28][CH2:29][O:30][CH2:31][CH2:32]2)[N:19]=1

Participants

Conditions

Temperature: 80 °C

Procedure

Potassium carbonate (36.0 g, 260.5 mmol) and cyclopropylmethyl bromide (20.2 g, 143.3 mmol) were added to an N,N-dimethylformamide suspension (400 ml) of 2-chloro-6-morpholin-4-yl-9H-purine (32.4 g; purity, approx. 96%; 130.2 mmol) at room temperature and the resulting mixture was stirred at 80° C. for 3 hours in a nitrogen atmosphere. The reaction mixture was left standing to cool, then poured into ethyl acetate, washed with saturated aqueous sodium hydrogen carbonate solution, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure and the resulting solid was washed with diethyl ether and collected by filtration to give the title compound (26.9 g, 70%) as a colorless acicular crystal. The mother liquor was further concentrated by the same procedure to give the secondary crystal of the title compound (7.68 g, 20%) as a white solid.

Workup

waitThe reaction mixture was left
temperatureto cool
washwashed with saturated aqueous sodium hydrogen carbonate solution
dry with materialdried over anhydrous sodium sulfate
filtrationAfter filtration
concentrationthe filtrate was concentrated under reduced pressure
washthe resulting solid was washed with diethyl ether
filtrationcollected by filtration

Sources & evidence

ORD record: ord-e8e21225cf81464a987a50e90ec1a3e1
Source dataset: uspto-grants-2012_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08309546B2

Reaction notes

Loading…