2,3,6-Trifluorophenylboronic acid → 5-amino-N-(5-((2S,5R,6R)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,3,6-trifluorophenyl)thiazole-4-carboxamide

HRID 522025Notes

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]([F:48])[C:42]=1B(O)O>>[NH2:32][C:4]1[S:3][C:2]([C:42]2[C:43]([F:48])=[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 41606152,3,6-Trifluorophenylboronic 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 867139155-amino-N-(5-((2S,5R,6R)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,3,6-trifluorophenyl)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 (2,3,6-trifluorophenyl)boronic acid gave 260. 1H NMR (400 MHz, DMSO-d6) δ 9.47 (s, 1H), 7.85 (s, 1H), 7.65-7.52 (m, 3H), 7.39-7.27 (m, 1H), 5.03-4.83 (m, 2H), 4.16-3.90 (m, 2H), 3.73 (s, 3H), 3.39 (dd, J=7.1, 4.6 Hz, 1H), 2.18 (ddd, J=15.1, 6.7, 3.5 Hz, 1H), 1.87 (dt, J=14.1, 10.3 Hz, 1H), 1.69 (dtd, J=18.1, 13.8, 11.5, 7.4 Hz, 2H). LCMS (ES+) m/z 485 (M+1).

Sources & evidence

ORD record: ord-01da9e052c6e4068a6127db44558a613
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328106B2

Reaction notes

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