Diisopropylethylamine → N-{5-chloro-2-{[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]amino}-6-[(5-methoxy-1H-pyrazol-3-yl)amino]pyrimidin-4-yl}-N,N',N'-trimethylsulfamide

HRID 415404Notes

Reaction equation

Cl[C:2]1[N:7]=[C:6]([N:8]([CH3:15])[S:9]([N:12]([CH3:14])[CH3:13])(=[O:11])=[O:10])[C:5]([Cl:16])=[C:4]([NH:17][C:18]2[CH:22]=[C:21]([O:23][CH3:24])[NH:20][N:19]=2)[N:3]=1.Cl.[F:26][C:27]1[CH:28]=[N:29][C:30]([C@@H:33]([NH2:35])[CH3:34])=[N:31][CH:32]=1.CCN(C(C)C)C(C)C>CCCCO>[Cl:16][C:5]1[C:6]([N:8]([CH3:15])[S:9]([N:12]([CH3:14])[CH3:13])(=[O:11])=[O:10])=[N:7][C:2]([NH:35][C@H:33]([C:30]2[N:31]=[CH:32][C:27]([F:26])=[CH:28][N:29]=2)[CH3:34])=[N:3][C:4]=1[NH:17][C:18]1[CH:22]=[C:21]([O:23][CH3:24])[NH:20][N:19]=1

Participants

Conditions

Temperature: 160 °C

Procedure

A microwave reaction vessel was charged with N-{2,5-dichloro-6-[(5-methoxy-1H-pyrazol-3-yl)amino]pyrimidin-4-yl}-N,N′,N′-trimethylsulfamide (Method 29, 44.1 mg, 0.112 mmol), (S)-1-(5-fluoropyrimidin-2-yl)ethanamine hydrochloride (Method 7, 39.5 mg, 0.223 mmol), and DIPEA (0.062 ml, 0.352 mmol). Anhydrous n-BuOH (1 ml) was added, and the tube was sealed and heated in a microwave reactor at 160° C. for 2 hours. The reaction mixture was purified by silica gel chromatography (by ISCO Combiflash with gradient EtOAc and hexane) to afford the title compound as a white solid (48.6 mg, 87%). LC-MS, 501 (M+1). 1H NMR (DMSO-d6, 400 MHz) δ 12.01 (s, 1H), 9.76 (s, 1H), 8.83 (s, 2H), 8.21 (s, 1H), 5.60 (s, 1H), 5.04-5.06 (m, 1H), 3.76 (s, 3H), 2.80 (s, 3H), 2.70 (s, 6H), 1.59 (d, 3H).

Workup

customA microwave reaction vessel
customthe tube was sealed
customThe reaction mixture was purified by silica gel chromatography (by ISCO Combiflash with gradient EtOAc and hexane)

Sources & evidence

ORD record: ord-531af947ec434708a9b3ab556f397bea
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088784B2

Reaction notes

Loading…