(2-Chloro-3-fluorophenyl)boronic acid → N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-6-(2-chloro-3-fluorophenyl)-5-fluoropicolinamide

HRID 521995Notes

Reaction equation

Br[C:2]1[N:7]=[C:6]([C:8]([NH:10][C:11]2[CH:12]=[N:13][N:14]([CH3:32])[C:15]=2[C@H:16]2[O:22][CH2:21][C@@H:20]([F:23])[C@H:19]([NH:24]C(=O)OC(C)(C)C)[CH2:18][CH2:17]2)=[O:9])[CH:5]=[CH:4][C:3]=1[F:33].[Cl:34][C:35]1[C:40]([F:41])=[CH:39][CH:38]=[CH:37][C:36]=1B(O)O>>[NH2:24][C@H:19]1[C@H:20]([F:23])[CH2:21][O:22][C@H:16]([C:15]2[N:14]([CH3:32])[N:13]=[CH:12][C:11]=2[NH:10][C:8](=[O:9])[C:6]2[CH:5]=[CH:4][C:3]([F:33])=[C:2]([C:36]3[CH:37]=[CH:38][CH:39]=[C:40]([F:41])[C:35]=3[Cl:34])[N:7]=2)[CH2:17][CH2:18]1

Participants

Reactant 2

HCID 22309459(2-Chloro-3-fluorophenyl)boronic acid

HCID 86713849tert-butyl ((3S,4R,7S)-7-(4-(6-bromo-5-fluoropicolinamido)-1-methyl-1H-pyrazol-5-yl)-3-fluorooxepan-4-yl)carbamate2×

Product 1

HCID 73438465N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-6-(2-chloro-3-fluorophenyl)-5-fluoropicolinamide

Procedure

Following the procedure for Example 101 starting from tert-butyl ((3S,4R,7S)-7-(4-(6-bromo-5-fluoropicolinamido)-1-methyl-1H-pyrazol-5-yl)-3-fluorooxepan-4-yl)carbamate (Intermediate 103), and replacing 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester with (2-chloro-3-fluorophenyl)boronic acid gave 227. 1H NMR (400 MHz, DMSO-d6) δ 10.18 (s, 1H), 8.28 (dd, J=8.6, 3.9 Hz, 1H), 8.12 (t, J=8.9 Hz, 1H), 7.89 (s, 1H), 7.64-7.45 (m, 3H), 4.81 (dd, J=10.3, 3.8 Hz, 1H), 4.20 (ddt, J=49.1, 5.7, 2.7 Hz, 1H), 4.05-3.80 (m, 2H), 3.75 (s, 3H), 3.09-2.95 (m, 1H), 2.10-1.99 (m, 1H), 1.82-1.64 (m, 1H), 1.66-1.56 (m, 2H), 1.53 (br, 2H). LCMS (ES+) m/z 480 (M+1).

Sources & evidence

ORD record: ord-b3e2794548cf48189b22663d0430750d
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328106B2

Reaction notes

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