Diisopropylethylamine → N-(4-(4-(5-methylthiazol-2-ylamino)-6-(3-(dimethylamino)azetidin-1-yl)pyrimidin-2ylthio)phenyl)cyclopropane carboxamide

HRID 473984Notes

Reaction equation

[CH3:1][C:2]1[S:6][C:5]([NH:7][C:8]2[CH:13]=[C:12](Cl)[N:11]=[C:10]([S:15][C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([CH:25]4[CH2:27][CH2:26]4)=[O:24])=[CH:18][CH:17]=3)[N:9]=2)=[N:4][CH:3]=1.Cl.Cl.[CH3:30][N:31]([CH3:36])[CH:32]1[CH2:35][NH:34][CH2:33]1.C(N(CC)C(C)C)(C)C>C(O)CCC>[CH3:1][C:2]1[S:6][C:5]([NH:7][C:8]2[CH:13]=[C:12]([N:34]3[CH2:35][CH:32]([N:31]([CH3:36])[CH3:30])[CH2:33]3)[N:11]=[C:10]([S:15][C:16]3[CH:21]=[CH:20][C:19]([NH:22][C:23]([CH:25]4[CH2:27][CH2:26]4)=[O:24])=[CH:18][CH:17]=3)[N:9]=2)=[N:4][CH:3]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A suspension of N-(4-(4-(5-methylthiazol-2-ylamino)-6-chloropyrimidin-2-ylthio)phenyl)cyclopropanecarboxamide (138 mg, 0.33 mmol), 3-dimethylaminoazetidine dihydrochloride (178 mg, 1.0 mmol), N,N-diisopropylethylamine (0.34 ml, 1.98 mmol) in n-butanol (10 ml) was heated at 90° C. for 17 h. Reaction mixture was then allowed to cool to room temperature, concentrated in vacuo. The crude product was purified on HPLC to give the title compound as an off-white solid (106 mg, 58%). 1H NMR (DMSO) 0.82-0.81 (4H, m), 1.87-1.81 (1H, m), 2.07 (3H, s), 2.78-2.77 (6H, m), 4.20 (5H, s), 5.56 (1H, s), 6.94 (1H, s), 7.52 (2H, d), 7.76 (2H, d), 10.55 (1H, s). MS (ES+): 482.

Workup

customReaction mixture
temperatureto cool to room temperature
concentrationconcentrated in vacuo
customThe crude product was purified on HPLC

Sources & evidence

ORD record: ord-1aa88ec64e9d4e379c0a7e0849e4d397
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637511B2

Reaction notes

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