2-Chloro-5-fluorobenzeneboronic acid → 5-amino-N-(5-((2S,5R,6R)-5-amino-6-methoxyoxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(5-chloro-2-fluorophenyl)thiazole-4-carboxamide

HRID 522045Notes

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.[Cl:41][C:42]1[CH:47]=[CH:46][C:45]([F:48])=[CH:44][C:43]=1B(O)O>>[NH2:33][C:4]1[S:3][C:2]([C:46]2[CH:47]=[C:42]([Cl:41])[CH:43]=[CH:44][C:45]=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 226481162-Chloro-5-fluorobenzeneboronic 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 867139345-amino-N-(5-((2S,5R,6R)-5-amino-6-methoxyoxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(5-chloro-2-fluorophenyl)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-chloro-5-fluorophenyl)boronic acid gave 281. 1H NMR (400 MHz, DMSO-d6) δ 9.62 (s, 1H), 8.12 (dd, J=6.4, 2.7 Hz, 1H), 7.79 (s, 1H), 7.55-7.39 (m, 4H), 5.07 (dd, J=7.0, 4.5 Hz, 1H), 3.99-3.84 (m, 2H), 3.72 (s, 3H), 3.52-3.43 (m, 1H), 3.33-3.24 (m, 1H), 3.15 (s, 3H), 2.33-2.22 (m, 1H), 1.82-1.52 (m, 4H). LCMS (ES+) m/z 495 (M+1).

Sources & evidence

ORD record: ord-bae9dfba5e6c47de89ec08ed056ef9bf
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328106B2

Reaction notes

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