(2,3-Difluorophenyl)boronic acid → 5-amino-N-(5-((2S,5R,6R)-5-amino-6-methoxyoxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,3-difluorophenyl)thiazole-4-carboxamide

HRID 521987Notes

Reaction equation

Br[C:2]1[S:3][C:4]([NH:33]C(=O)OC(C)(C)C)=[C:5]([C:7](=[O:32])[NH:8][C:9]2[CH:10]=[N:11][N:12]([CH3:31])[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]([O:29][CH3:30])[CH2:16][O:15]2)[N:6]=1.[F:41][C:42]1[C:47]([F:48])=[CH:46][CH:45]=[CH:44][C:43]=1B(O)O>>[NH2:33][C:4]1[S:3][C:2]([C:46]2[CH:45]=[CH:44][CH:43]=[C:42]([F:41])[C:47]=2[F:48])=[N:6][C:5]=1[C:7]([NH:8][C:9]1[CH:10]=[N:11][N:12]([CH3:31])[C:13]=1[C@@H:14]1[CH2:20][CH2:19][C@@H:18]([NH2:21])[C@@H:17]([O:29][CH3:30])[CH2:16][O:15]1)=[O:32]

Participants

Reactant 2

HCID 2734333(2,3-Difluorophenyl)boronic acid

HCID 86713844tert-Butyl N-[2-bromo-4-[[5-[(2S,5R,6R)-5-(tert-butoxycarbonylamino)-6-methoxy-oxepan-2-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate2×

Product 1

HCID 867138925-amino-N-(5-((2S,5R,6R)-5-amino-6-methoxyoxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,3-difluorophenyl)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-methoxy-oxepan-2-yl]-1-methyl-pyrazol-4-yl]carbamoyl]thiazol-5-yl]carbamate (Intermediate 98), and replacing 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester with (2,3-difluorophenyl)boronic acid gave 219. 1H NMR (400 MHz, DMSO-d6) δ 9.60 (s, 1H), 7.90-7.82 (m, 2H), 7.56-7.42 (m, 3H), 7.38-7.30 (m, 1H), 5.07 (t, J=5.7 Hz, 1H), 3.98-3.90 (m, 1H), 3.88-3.80 (m, 1H), 3.71 (s, 3H), 3.50-3.45 (m, 1H), 3.14 (d, J=1.5 Hz, 3H), 2.36-2.31 (m, 2H), 1.76-1.71 (m, 1H), 1.63-1.58 (m, 4H), 1.50-1.45 (m, 1H). LCMS (ES+) m/z 479 (M+1).

Sources & evidence

ORD record: ord-54995b3121a04394a078f7bc38905d6e
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328106B2

Reaction notes

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