Boron tribromide → HCID 17747249, compound
Reaction equation
[CH:1]1([S:4]([N:7]2[CH2:12][CH2:11][CH:10]([NH:13][C:14]3[N:19]=[C:18]([C:20]4[N:27]5[C:23]([S:24][CH:25]=[CH:26]5)=[N:22][C:21]=4[C:28]4[CH:33]=[CH:32][C:31]([F:34])=[C:30]([O:35]C)[CH:29]=4)[CH:17]=[CH:16][N:15]=3)[CH2:9][CH2:8]2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.B(Br)(Br)Br>C(Cl)Cl>[CH:1]1([S:4]([N:7]2[CH2:8][CH2:9][CH:10]([NH:13][C:14]3[N:19]=[C:18]([C:20]4[N:27]5[C:23]([S:24][CH:25]=[CH:26]5)=[N:22][C:21]=4[C:28]4[CH:33]=[CH:32][C:31]([F:34])=[C:30]([OH:35])[CH:29]=4)[CH:17]=[CH:16][N:15]=3)[CH2:11][CH2:12]2)(=[O:5])=[O:6])[CH2:2][CH2:3]1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
The N-[1-(cyclopropylsulfonyl)piperidin-4-yl]-4-[6-(4-fluoro-3-methoxyphenyl)imidazo[2,1-b][1,3]thiazol-5-yl]pyrimidin-2-amine (0.226 g, 0.43 mmol) in methylene chloride (8 ml) was cooled to −78° C. and slowly treated with 1 molar solution of boron tribromide in methylene chloride (3.4 ml). The reaction mixture was kept at −78° C. for one hour then was allowed to warm to room temperature for two hours. The mixture was quenched by the addition of methanol (900 μl) at −78° C. and was stirred at room temperature for an additional hour. The mixture was diluted with methylene chloride (100 ml) and washed with three portions of 25 ml of saturated sodium bicarbonate solution, two portions of 25 ml of water and two portions of 25 ml of saturated sodium chloride solution. The organic phase was dried over sodium sulfate and concentrated in vacuo, giving a yellow solid. The crude product was purified by flash chromatography (ethyl acetate), affording 0.19 g (86%) of the title compound as a beige solid. M.p.=224-225° C. 400 MHz 1H NMR (DMSO-d6 at 60° C.) δ: 9.82 (s, 1H), 8.67 (br. s, 1H), 8.12 (d, J=5.5 Hz, 1H), 7.43 (d, J=4.3 Hz, 1H), 7.25-7.14 (m, 3H), 6.99 (ddd, J=8.2, 4.3, 2.0 Hz, 1H), 6.41 (d, J=5.1 Hz, 1H), 3.95-3.84 (m, 1H), 3.68-3.60 (m, 2H), 3.00 (td, J=11.9, 2.7 Hz, 2H), 2.59-2.52 (m, 1H), 2.06-1.98 (m, 2H), 1.66-1.54(m, 2H), 1.04-0.92 (m, 4H). LCMS: 515 [M+H]. Calc. for C23H23N6O3S2F.0.53 diethyl ether.0.17 water: C, 53.46; H, 4.93; N, 14.89. Found C, 53.46; H, 4.60; N, 14.88.