Reaction equation
[NH2:1][C:2]1[C:7]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[C:10]([F:17])[CH:9]=2)=[CH:6][C:5]([CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[CH:4][N:3]=1.[CH3:24][C:25]1[N:30]=[C:29]([CH2:31][NH2:32])[CH:28]=[CH:27][CH:26]=1.CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>CN(C=O)C>[NH2:1][C:2]1[C:7]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([NH:32][CH2:31][C:29]3[CH:28]=[CH:27][CH:26]=[C:25]([CH3:24])[N:30]=3)=[O:14])=[C:10]([F:17])[CH:9]=2)=[CH:6][C:5]([CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[CH:4][N:3]=1Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
To a vial were charged with 4-(2-amino-5-(tetrahydro-2H-pyran-4-yl)pyridin-3-yl)-2-fluorobenzoic acid (20 mg, 0.063 mmol), (6-methylpyridin-2-yl)methanamine (11.6 mg, 0.095 mmol), DIEA (28 μL, 0.158 mmol), PyBOP (65.8, 0.126 mmol) and DMF (0.5 mL). The mixture was stirred at room temperature for 10 min. The reaction mixture was then purified by preparative HPLC, and product fractions were combined, frozen and lyophilized to afford 4-(2-amino-5-(tetrahydro-2H-pyran-4-yl)pyridin-3-yl)-2-fluoro-N-((6-methylpyridin-2-yl)methyl)benzamide as a white powder. LCMS (m/z) 421.3 (MH+) 0.41 min. 1H NMR (DMSO-d6) δ ppm 8.99 (d, J=3.1 Hz, 1H), 7.95-7.83 (m, 3H), 7.79 (t, J=7.6 Hz, 1H), 7.53 (d, J=11.7 Hz, 2H), 7.44 (dd, J=8.0, 1.4 Hz, 1H), 7.24 (d, J=7.4 Hz, 2H), 4.60 (d, J=5.5 Hz, 2H), 4.02-3.88 (m, 2H), 3.40 (td, J=11.2, 2.7 Hz, 3H), 2.88-2.71 (m, 1H), 2.51 (br. s., 3H), 1.82-1.58 (m, 4H).
Workup
- customThe reaction mixture was then purified by preparative HPLC, and product fractions
- temperaturefrozen
Sources & evidence
- ORD record
- ord-fbf78b4cd7604e819ab8198698edfbae
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09242996B2
Linked notes
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