3-(3,5-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxetan-3-ol → N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,6-difluoro-4-(3-hydroxyoxetan-3-yl)phenyl)thiazole-4-carboxamide

HRID 521992Notes

Reaction equation

HRID 521992 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.[F:32][C:33]1[CH:34]=[C:35]([C:49]2([OH:53])[CH2:52][O:51][CH2:50]2)[CH:36]=[C:37]([F:48])[C:38]=1B1OC(C)(C)C(C)(C)O1>>[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[C:33]([F:32])=[CH:34][C:35]([C:49]4([OH:53])[CH2:50][O:51][CH2:52]4)=[CH:36][C:37]=3[F:48])[S:3][CH:4]=2)=[O:8])[CH2:16][CH2:17]1

Participants

3

Reactant 2

HCID 706556493-(3,5-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxetan-3-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 86713896N-(5-((2S,5R,6S)-5-amino-6-fluorooxepan-2-yl)-1-methyl-1H-pyrazol-4-yl)-2-(2,6-difluoro-4-(3-hydroxyoxetan-3-yl)phenyl)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 3-(3,5-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxetan-3-ol (see US2012/225062) gave 224. LCMS (ES+) m/z 524 (M+1).

Sources & evidence

ORD record
ord-e3aa0488d62b4aacbd8c6e484bc6b08e
Source dataset
uspto-grants-2016_05
Patent number
US09328106B2

Reaction notes

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