2-(Trifluoromethyl)benzeneboronic acid → 5-amino-N-(5-((2S,5R,6R)-5-amino-6-methoxyoxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2-(trifluoromethyl)phenyl)thiazole-4-carboxamide

HRID 521988Notes

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]([F:53])([F:52])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1B(O)O>>[NH2:33][C:4]1[S:3][C:2]([C:44]2[CH:45]=[CH:46][CH:47]=[CH:48][C:43]=2[C:42]([F:53])([F:52])[F:41])=[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 27343872-(Trifluoromethyl)benzeneboronic 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 867138935-amino-N-(5-((2S,5R,6R)-5-amino-6-methoxyoxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2-(trifluoromethyl)phenyl)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-(trifluoromethyl)phenyl)boronic acid gave 220. 1H NMR (400 MHz, DMSO-d6) δ 9.39 (s, 1H), 7.93-7.86 (m, 2H), 7.81-7.63 (m, 3H), 7.44 (s, 2H), 5.04 (t, J=5.1 Hz, 1H), 3.73-3.57 (m, 5H), 3.29-3.15 (m, 2H), 2.74 (s, 3H), 2.48-2.35 (m, 1H), 1.65-1.47 (m, 3H), 1.41 (br, 2H). LCMS (ES+) m/z 511 (M+1).

Sources & evidence

ORD record: ord-aa87734448e9425ba06c8a2f26156fd5
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328106B2

Reaction notes

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