(1-Isopropyl-1H-pyrazol-4-yl)boronic acid → 5-amino-N-(5-((2S,5R,6R)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(1-isopropyl-1H-pyrazol-4-yl)thiazole-4-carboxamide

HRID 522021Notes

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.[CH:40]([N:43]1[CH:47]=[C:46](B(O)O)[CH:45]=[N:44]1)([CH3:42])[CH3:41]>>[NH2:32][C:4]1[S:3][C:2]([C:46]2[CH:45]=[N:44][N:43]([CH:40]([CH3:42])[CH3:41])[CH:47]=2)=[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 53216602(1-Isopropyl-1H-pyrazol-4-yl)boronic 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 867139115-amino-N-(5-((2S,5R,6R)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(1-isopropyl-1H-pyrazol-4-yl)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 (1-isopropyl-1H-pyrazol-4-yl)boronic acid gave 256. 1H NMR (400 MHz, DMSO-d6) δ 9.37 (s, 1H), 8.15 (s, 1H), 7.83 (s, 1H), 7.77 (s, 1H), 7.25 (s, 2H), 5.12-4.80 (m, 2H), 4.60-4.45 (m, 1H), 4.18-3.95 (m, 2H), 3.72 (s, 3H), 3.38-3.26 (m, 1H), 2.33-2.22 (m, 1H), 1.83-1.56 (m, 5H), 1.44 (d, J=6.7 Hz, 6H). LCMS (ES+) m/z 463 (M+1).

Sources & evidence

ORD record: ord-733c5a187cb147238b29fdf476b7f50f
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328106B2

Reaction notes

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