2-methyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propan-2-ol → N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)thiazole-4-carboxamide

HRID 521996Notes

Reaction equation

HRID 521996 reaction equation
Br[C:2]1[S:3][CH:4]=[C:5]([C:7]([NH:9][C:10]2[CH:11]=[N:12][N:13]([CH3:31])[C:14]=2[C@H:15]2[O:21][CH2:20][C@@H:19]([F:22])[C@H:18]([NH:23]C(=O)OC(C)(C)C)[CH2:17][CH2:16]2)=[O:8])[N:6]=1.[CH3:32][C:33]([OH:50])([CH3:49])[CH2:34][N:35]1[CH:39]=[C:38](B2OC(C)(C)C(C)(C)O2)[CH:37]=[N:36]1>>[NH2:23][C@H:18]1[C@H:19]([F:22])[CH2:20][O:21][C@H:15]([C:14]2[N:13]([CH3:31])[N:12]=[CH:11][C:10]=2[NH:9][C:7]([C:5]2[N:6]=[C:2]([C:38]3[CH:37]=[N:36][N:35]([CH2:34][C:33]([OH:50])([CH3:49])[CH3:32])[CH:39]=3)[S:3][CH:4]=2)=[O:8])[CH2:16][CH2:17]1

Participants

3

Reactant 2

HCID 582041312-methyl-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl]propan-2-olHCID 86713845tert-butyl ((3S,4R,7S)-7-(4-(2-bromothiazole-4-carboxamido)-1-methyl-1H-pyrazol-5-yl)-3-fluorooxepan-4-yl)carbamate2×

Product 1

HCID 73438466N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(1-(2-hydroxy-2-methylpropyl)-1H-pyrazol-4-yl)thiazole-4-carboxamide

Procedure

Following the procedure for Example 101 starting from tert-butyl ((3S,4R,7S)-7-(4-(2-bromothiazole-4-carboxamido)-1-methyl-1H-pyrazol-5-yl)-3-fluorooxepan-4-yl)carbamate (Intermediate 99), and replacing 3,6-dihydro-2H-pyran-4-boronic acid pinacol ester with 2-methyl-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)propan-2-ol (see US2011/76291) gave 228. 1H NMR (400 MHz, DMSO-d6) δ 9.77 (s, 1H), 8.32 (s, 1H), 8.22 (s, 1H), 8.04 (s, 1H), 7.88 (s, 1H), 4.88 (dd, J=10.0, 3.9 Hz, 1H), 4.69-4.42 (m, 1H), 4.39-4.24 (m, 1H), 4.17-3.95 (m, 4H), 3.77 (s, 3H), 2.15-2.05 (m, 1H), 1.89-1.68 (m, 3H), 1.10 (d, J=4.4 Hz, 6H). LCMS (ES+) m/z 478 (M+1).

Sources & evidence

ORD record
ord-5fdde25afd42471fb19b3754a23fe85f
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

Loading…