2-(Cyclopent-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane → 5-amino-N-(5-((2S,5R,6R)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(cyclopent-1-en-1-yl)thiazole-4-carboxamide

HRID 522036Notes

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.[C:40]1(B2OC(C)(C)C(C)(C)O2)[CH2:44][CH2:43][CH2:42][CH:41]=1>>[NH2:32][C:4]1[S:3][C:2]([C:40]2[CH2:44][CH2:43][CH2:42][CH:41]=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 154866112-(Cyclopent-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

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 867139265-amino-N-(5-((2S,5R,6R)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(cyclopent-1-en-1-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 2-(cyclopent-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane gave 271. 1H NMR (400 MHz, DMSO-d6) δ 9.25 (s, 1H), 7.80 (s, 1H), 7.35 (br, J=8.5 Hz, 2H), 6.21-6.14 (m, 1H), 5.22-4.76 (m, 2H), 4.22-3.94 (m, 2H), 3.71 (s, 3H), 3.53-3.40 (m, 1H), 2.76-2.66 (m, 2H), 2.22-2.10 (m, 1H), 2.02-1.87 (m, 3H), 1.84-1.67 (m, 2H). LCMS (ES+) m/z 421 (M+1).

Sources & evidence

ORD record: ord-73b13e0c188e4d37adeb192303f02eee
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328106B2

Reaction notes

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