N-bromobutanimide → 2-[(6-chloro-2-methylpyrimidin-4-yl)amino]-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide

HRID 1725553Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[C:3]=1[NH:9][C:10](=[O:16])/[CH:11]=[CH:12]/OCC.C1C(=O)N(Br)C(=O)C1.[Cl:25][C:26]1[N:31]=[C:30]([CH3:32])[N:29]=[C:28]([NH:33][C:34]([NH2:36])=[S:35])[CH:27]=1>C1COCC1.O>[Cl:25][C:26]1[N:31]=[C:30]([CH3:32])[N:29]=[C:28]([NH:33][C:34]2[S:35][C:11]([C:10]([NH:9][C:3]3[C:4]([CH3:8])=[CH:5][CH:6]=[CH:7][C:2]=3[Cl:1])=[O:16])=[CH:12][N:36]=2)[CH:27]=1

Participants

Conditions

Temperature: 21 °C

Procedure

To a slurry of (E)-N-(2-chloro-6-methylphenyl)-3-ethoxyacrylamide 5B (120 mg, 0.50 mmol) in THF (0.75 ml) and water (0.5 mL) was added NBS (98 mg, 0.55 mmol) at 0° C. The mixture was warmed and stirred at 20-22° C. for 3h. To this was added 1-(6-chloro-2-methylpyrimidin-4-yl)thiourea 5A (100 mg, 0.49 mmol), and the slurry heated and stirred at reflux for 2h. The slurry was cooled to 20-22° C. and the solid collected by vacuum filtration giving 140 mg (71% yield) of 2-(6-chloro-2-methylpyrimidin-4-ylamino)-N-(2-chloro-6-methylphenyl)thiazole-5-carboxamide 5D. 1H NMR (400 MHz, DMSO-d6) δ 2.23 (s, 3H), 2.58 (s, 3H), 6.94 (s, 1H), 7.18-7.34, (m, 2H, J=7.5), 7.34-7.46 (d, 1H, J=7.5), 8.31 (s, 1H), 10.02 (s, 1H), 12.25 (s, 1H).

Workup

temperatureThe mixture was warmed
temperaturethe slurry heated
stirringstirred
temperatureat reflux for 2h
temperatureThe slurry was cooled to 20-22° C.
filtrationthe solid collected by vacuum filtration

Sources & evidence

ORD record: ord-a79fd813546d425a868c6055465bb37d
Source dataset: uspto-grants-2009_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07491725B2

Reaction notes

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