5-(6-Amino-5-bromopyridin-3-yl)-1-methylpiperidin-2-one → 4-(2-amino-5-(1-methyl-6-oxopiperidin-3-yl)pyridin-3-yl)-N-((S)-1-(3-chlorophenyl)-2-hydroxyethyl)-2-fluorobenzamide
Reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([CH:8]2[CH2:13][N:12]([CH3:14])[C:11](=[O:15])[CH2:10][CH2:9]2)=[CH:4][C:3]=1Br.[Cl:17][C:18]1[CH:19]=[C:20]([C@H:24]([NH:27][C:28]([C:30]2[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][C:31]=2[F:39])=[O:29])[CH2:25][OH:26])[CH:21]=[CH:22][CH:23]=1>>[NH2:1][C:2]1[C:3]([C:33]2[CH:34]=[CH:35][C:30]([C:28]([NH:27][C@@H:24]([C:20]3[CH:21]=[CH:22][CH:23]=[C:18]([Cl:17])[CH:19]=3)[CH2:25][OH:26])=[O:29])=[C:31]([F:39])[CH:32]=2)=[CH:4][C:5]([CH:8]2[CH2:9][CH2:10][C:11](=[O:15])[N:12]([CH3:14])[CH2:13]2)=[CH:6][N:7]=1Participants
3
Reactant 2
Product 1
Procedure
Following Step 6 in Scheme 47, using 5-(6-amino-5-bromopyridin-3-yl)-1-methylpiperidin-2-one and (S)-(4-((1-(3-chlorophenyl)-2-hydroxyethyl)carbamoyl)-3-fluorophenyl)boronic acid, 4-(2-amino-5-(1-methyl-6-oxopiperidin-3-yl)pyridin-3-yl)-N—((S)-1-(3-chlorophenyl)-2-hydroxyethyl)-2-fluorobenzamide was obtained (33%). LCMS (m/z): 497.2 (MH+), 0.61 min; 1H NMR (400 MHz, CD3OD) δ ppm 8.70 (m, 1H), 7.98 (m, 1H), 7.88 (m, 2H), 7.44 (m, 3H), 7.36 (m, 2H), 7.30 (m, 1H), 5.19 (m, 1H), 3.88 (m, 2H), 3.51 (m, 2H), 3.21 (m, 1H), 2.97 (s, 3H), 2.50 (m, 2H), 2.07 (m, 2H). The diastereomeric mixture was separated by chiral SFC (ChiralPak 5mic AD column, 4.6×100 (mm), EtOH+0.1% DEA=40%, 5 ml/min). The polar diastereomer, 4-(2-amino-5-((R)-1-methyl-6-oxopiperidin-3-yl)pyridin-3-yl)-N—((S)-1-(3-chlorophenyl)-2-hydroxyethyl)-2-fluorobenzamide was obtained at Rt=2.22 min. LCMS (m/z): 497.2 (MH+), 0.61 min. The less polar diastereomer, 4-(2-amino-5-((S)-1-methyl-6-oxopiperidin-3-yl)pyridin-3-yl)-N—((S)-1-(3-chlorophenyl)-2-hydroxyethyl)-2-fluorobenzamide was obtained at Rt=3.09 min. LCMS (m/z): 497.3 (MH+), 0.59 min.