Boron tribromide → HCID 86297634, compound
Reaction equation
C[O:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[C:8]([C:12]#[N:13])[NH:9]2)=[CH:5][C:4]=1[CH2:14][N:15]1[CH2:20][CH2:19][CH:18]([NH:21][C:22]2[C:23]3[CH:30]=[C:29]([CH2:31][C:32]([F:35])([F:34])[F:33])[S:28][C:24]=3[N:25]=[CH:26][N:27]=2)[CH2:17][CH2:16]1.B(Br)(Br)Br.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[OH:2][C:3]1[CH:11]=[C:10]2[C:6]([CH:7]=[C:8]([C:12]#[N:13])[NH:9]2)=[CH:5][C:4]=1[CH2:14][N:15]1[CH2:16][CH2:17][CH:18]([NH:21][C:22]2[C:23]3[CH:30]=[C:29]([CH2:31][C:32]([F:34])([F:35])[F:33])[S:28][C:24]=3[N:25]=[CH:26][N:27]=2)[CH2:19][CH2:20]1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
500 mg of 6-methoxy-5-((4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1H-indole-2-carbonitrile (1 mmol) was slowly added to 5 mL of 1M BBr3 in DCM at 0 degrees and reaction mixture was brought to RT. After 4days ice was added to reaction mixture in the presence of sodium bicarbonate. Volatile organic was evaporated and the residue was partitioned between water and ethyl acetate-methanol 10:1. Organic layer was evaporated with silica gel and loaded on the column. The product was eluted with hexane-ethyl acetate-methanol 1:1:0.1, evaporation of fractions produced 300 mg of 6-hydroxy-5-((4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1H-indole-2-carbonitrile (Compound 182). Its monohydrochloride salt was obtained by adding 1 equivalent of 1N HCl solution in diethyl ether to a solution of compound in ethanol. Monohydrochloride salt exists as a mixture of rotomers in approximate ratio 10:1, NMR is described for the major one: 1H NMR (600 MHz, MeOD-d4): 8.70 (s, 1H), 7.81 (s, 1H), 7.77 (s, 1H), 7.21 (s, 1H), 6.98 (s, 1H), 4.64 (m, 1H), 4.48 (s, 1H), 4.01 (q, 2H, J=10.3 Hz), 3.66 (m, 2H), 3.35 (m, 2H), 2.37 (m, 2H), 2.12 (m, 2H). 13C NMR (150 MHz, MeOD-d4): δC 157.64, 156.62, 153.92, 141.09, 130.54, 127.75, 127.48, 125.65, 121.96, 121.59, 118.27, 115.23, 114.85, 113.98, 107.11, 97.45, 57.78, 52.88, 47.29, 35.54 (q, J=33 Hz), 29.95. ESI MS [MH+]: 487.1519.