Ethyl Acetate → 6-Cyclopropylmethoxymethyl-3-[4-(3-dimethylamino-pyrrolidin-1-yl)-phenyl]-3H-thieno[3,2-d]pyrimidin-4-one

HRID 72244Notes

Reaction equation

[CH3:1][N:2]([CH3:26])[CH:3]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[CH:12][C:11]([N:14]3[C:19](=[O:20])[C:18]4[S:21][C:22]([CH2:24][OH:25])=[CH:23][C:17]=4[N:16]=[CH:15]3)=[CH:10][CH:9]=2)[CH2:4]1.[K].CC(C)([O-])C.[CH:33]1([CH2:36]Br)[CH2:35][CH2:34]1.C(OCC)(=O)C>CN(C=O)C.O>[CH:33]1([CH2:36][O:25][CH2:24][C:22]2[S:21][C:18]3[C:19](=[O:20])[N:14]([C:11]4[CH:10]=[CH:9][C:8]([N:5]5[CH2:6][CH2:7][CH:3]([N:2]([CH3:26])[CH3:1])[CH2:4]5)=[CH:13][CH:12]=4)[CH:15]=[N:16][C:17]=3[CH:23]=2)[CH2:35][CH2:34]1

Participants

Conditions

Temperature: 0 °C

Procedure

A mixture of 3-[4-(3-dimethylamino-pyrrolidin-1-yl)-phenyl]-6-hydroxymethyl-3H-thieno[3,2-d]pyrimidin-4-one (20.0 mg) and potassium-tert.-butoxide (7.65 mg) in DMF (0.3 mL) was stirred at 0° C. for 5 min. Then cyclopropylmethylbromide (11.28 mg) was added. The solution was warmed to room temperature and stirred for 2 h. Then ethyl acetate and water were added. The aqueous phase was extracted several times with ethyl acetate, the combined organic phases dried over sodium sulfate and the solvent removed in vacuo. The crude product was purified by preparative HPLC. The product with the molecular weight of 424.56 (C23H28N4O2S) was obtained in this way; MS (ESI): 425 (M+H+).

Workup

temperatureThe solution was warmed to room temperature
stirringstirred for 2 h
extractionThe aqueous phase was extracted several times with ethyl acetate
dry with materialthe combined organic phases dried over sodium sulfate
customthe solvent removed in vacuo
customThe crude product was purified by preparative HPLC
customThe product with the molecular weight of 424.56 (C23H28N4O2S) was obtained in this way

Sources & evidence

ORD record: ord-b2939d550b4b4562a249b2ee576eb368
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08828991B2

Reaction notes

Loading…