1-Hydroxybenzotriazole → 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(3-chlorobenzyl)-2-fluorobenzamide
Reaction equation
[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[C:16]([F:23])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:6][N:7]=1.[Cl:24][C:25]1[CH:26]=[C:27]([CH2:31][NH2:32])[CH:28]=[CH:29][CH:30]=1.C1CN([P+](Br)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1>C1COCC1>[NH2:1][C:2]1[C:3]([C:14]2[CH:22]=[CH:21][C:17]([C:18]([NH:32][CH2:31][C:27]3[CH:28]=[CH:29][CH:30]=[C:25]([Cl:24])[CH:26]=3)=[O:20])=[C:16]([F:23])[CH:15]=2)=[N:4][C:5]([CH:8]2[CH2:9][CH2:10][O:11][CH2:12][CH2:13]2)=[CH:6][N:7]=1Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-2-fluorobenzoic acid (17 mg, 0.054 mmol) and (3-chlorophenyl)methanamine (8.34 mg, 0.059 mmol) in THF (268 μL) was added PyBroP (27.5 mg, 0.059 mmol), DIEA (28.1 μL, 0.161 mmol) and HOBT (9.02 mg, 0.059 mmol). The reaction mixture was stirred overnight at room temperature. All volatile material was removed in vacuo and dissolved in DCM. The crude product dissolved in DCM was loaded to flash chromatography column (gradient EtOAc in heptane) providing 4-(3-amino-6-(tetrahydro-2H-pyran-4-yl)pyrazin-2-yl)-N-(3-chlorobenzyl)-2-fluorobenzamide in 87% yield. LCMS (m/z): 441.1 (MH+), 0.79 min. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.92 (s, 1H), 7.74 (m, 1H), 7.63 (m, 2H), 7.35 (m, 4H), 6.14 (s, 1H), 4.48 (m, 2H), 3.92 (m, 2H), 3.43 (m, 2H), 1.73 (m, 4H).
Workup
- customAll volatile material was removed in vacuo
- dissolutiondissolved in DCM
- dissolutionThe crude product dissolved in DCM
Sources & evidence
- ORD record
- ord-94109d3576e0428b8ddd5d3995517011
- Source dataset
- uspto-grants-2016_01
- Patent number
- US09242996B2
Reaction notes
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