3-Chloro-2-fluorophenylboronic Acid → 5-amino-N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(3-chloro-2-fluorophenyl)thiazole-4-carboxamide

HRID 522073Notes

Reaction equation

Br[C:2]1[S:3][C:4]([NH:32]C(=O)OC(C)(C)C)=[C:5]([C:7](=[O:31])[NH:8][C:9]2[CH:10]=[N:11][N:12]([CH3:30])[C:13]=2[C@@H:14]2[CH2:20][CH2:19][C@@H:18]([NH:21]C(OC(C)(C)C)=O)[C@H:17]([F:29])[CH2:16][O:15]2)[N:6]=1.[Cl:40][C:41]1[C:42]([F:50])=[C:43](B(O)O)[CH:44]=[CH:45][CH:46]=1>>[NH2:32][C:4]1[S:3][C:2]([C:43]2[CH:44]=[CH:45][CH:46]=[C:41]([Cl:40])[C:42]=2[F:50])=[N:6][C:5]=1[C:7]([NH:8][C:9]1[CH:10]=[N:11][N:12]([CH3:30])[C:13]=1[C@@H:14]1[CH2:20][CH2:19][C@@H:18]([NH2:21])[C@H:17]([F:29])[CH2:16][O:15]1)=[O:31]

Participants

Reactant 2

HCID 162171583-Chloro-2-fluorophenylboronic Acid

HCID 86713840tert-butyl N-[2-bromo-4-[[5-[(2S,5R,6S)-5-(tert-butoxycarbonylamino)-6-fluoro-oxepan-2-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate2×

Product 1

HCID 867139655-amino-N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(3-chloro-2-fluorophenyl)thiazole-4-carboxamide

Procedure

Following the procedure for Example 101 starting from tert-butyl N-[2-bromo-4-[[5-[(2S,5R,6S)-5-(tert-butoxycarbonylamino)-6-fluoro-oxepan-2-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate (Intermediate 95), and replacing 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester with (3-chloro-2-fluorophenyl)boronic acid gave 338. 1H NMR (400 MHz, DMSO-d6) δ 9.34 (s, 1H), 8.47-8.06 (m, 1H), 7.86 (s, 1H), 7.66-7.55 (m, 1H), 7.52 (s, 2H), 7.30 (t, J=8.1 Hz, 1H), 4.83 (dd, J=10.5, 3.6 Hz, 1H), 4.58-4.37 (m, 1H), 4.36-4.22 (m, 1H), 4.18-3.97 (m, 1H), 3.76 (s, 3H), 2.10-2.00 (m, 1H), 1.89-1.60 (m, 4H). LCMS (ES+) m/z 483 (M+1).

Sources & evidence

ORD record: ord-13ae94c99c6545f38a37edeb1f989b70
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328106B2

Reaction notes

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