2,3-Difluoro-6-methoxyphenylboronic acid → 5-amino-N-(5-((2S,5R,6R)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,3-difluoro-6-methoxyphenyl)thiazole-4-carboxamide

HRID 522041Notes

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.[F:40][C:41]1[C:46]([F:47])=[CH:45][CH:44]=[C:43]([O:48][CH3:49])[C:42]=1B(O)O>>[NH2:32][C:4]1[S:3][C:2]([C:42]2[C:43]([O:48][CH3:49])=[CH:44][CH:45]=[C:46]([F:47])[C:41]=2[F:40])=[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 43727862,3-Difluoro-6-methoxyphenylboronic acid

HCID 86713830tert-butyl N-[2-bromo-4-[[5-[(2S,5R,6R)-5-(tert-butoxycarbonylamino)-6-fluoro-oxepan-2-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate2×

Product 1

HCID 867139305-amino-N-(5-((2S,5R,6R)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,3-difluoro-6-methoxyphenyl)thiazole-4-carboxamide

Procedure

Following the procedure for Example 101 starting from tert-butyl N-[2-bromo-4-[[5-[(2S,5R,6R)-5-(tert-butoxycarbonylamino)-6-fluoro-oxepan-2-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate (Intermediate 88), and replacing 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester with (2,3-difluoro-6-methoxyphenyl)boronic acid gave 277. 1H NMR (400 MHz, DMSO-d6) δ 9.42 (s, 1H), 7.84 (s, 1H), 7.47 (t, J=9.4 Hz, 1H), 7.39 (s, 2H), 7.01 (ddd, J=9.4, 4.0, 1.9 Hz, 1H), 5.02-4.76 (m, 2H), 4.18-3.93 (m, 2H), 3.92 (s, 3H), 3.72 (s, 3H), 2.23-2.13 (m, 1H), 1.90-1.60 (m, 4H). LCMS (ES+) m/z 497 (M+1).

Sources & evidence

ORD record: ord-828cafe46a6d4e7d8477a7d13b11dce9
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328106B2

Reaction notes

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