(2,5-Difluorophenyl)boronic acid → 5-Amino-N-(1-(2,2-difluoroethyl)-5-(4-hydroxyazepan-1-yl)-1H-pyrazol-4-yl)-2-(2,5-difluorophenyl)thiazole-4-carboxamide

HRID 1915852Notes

Reaction equation

HRID 1915852 reaction equation
Br[C:2]1[S:3][C:4]([NH:27]C(=O)OC(C)(C)C)=[C:5]([C:7](=[O:26])[NH:8][C:9]2[CH:10]=[N:11][N:12]([CH2:22][CH:23]([F:25])[F:24])[C:13]=2[N:14]2[CH2:20][CH2:19][CH2:18][CH:17]([OH:21])[CH2:16][CH2:15]2)[N:6]=1.[F:35][C:36]1[CH:41]=[CH:40][C:39]([F:42])=[CH:38][C:37]=1B(O)O>>[NH2:27][C:4]1[S:3][C:2]([C:40]2[CH:41]=[C:36]([F:35])[CH:37]=[CH:38][C:39]=2[F:42])=[N:6][C:5]=1[C:7]([NH:8][C:9]1[CH:10]=[N:11][N:12]([CH2:22][CH:23]([F:24])[F:25])[C:13]=1[N:14]1[CH2:20][CH2:19][CH2:18][CH:17]([OH:21])[CH2:16][CH2:15]1)=[O:26]

Participants

3

Reactant 2

HCID 2734335(2,5-Difluorophenyl)boronic acidHCID 86679969tert-butyl 2-bromo-4-(1-(2,2-difluoroethyl)-5-(4-hydroxyazepan-1-yl)-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate

Product 1

HCID 736028625-Amino-N-(1-(2,2-difluoroethyl)-5-(4-hydroxyazepan-1-yl)-1H-pyrazol-4-yl)-2-(2,5-difluorophenyl)thiazole-4-carboxamideYield 57.6%

Procedure

Following the procedure for Example 105, tert-butyl 2-bromo-4-(1-(2,2-difluoroethyl)-5-(4-hydroxyazepan-1-yl)-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate (130 mg, 0.23 mmol) and 2,5-difluorobenzeneboronic acid (55 mg, 0.35 mmol) were reacted to give 118 as a dark green solid (66 mg, 57% over two steps). 1H NMR (400 MHz, d4-MeOD) δ 8.10-8.00 (m, 1H), 7.68 (s, 1H), 7.30-7.20 (m, 1H), 7.19-7.11 (m, 1H), 6.24 (tt, J=55.6, 4.2 Hz, 1H), 4.51-4.40 (m, 2H), 4.01-3.92 (m, 1H), 3.45-3.30 (m, 2H), 3.31-3.16 (m, 3H), 2.13-1.91 (m, 2H), 1.90-1.67 (m, 2H). LCMS (ES+) m/z 499 (M+1).

Workup

  1. customwere reacted

Sources & evidence

ORD record
ord-6b2d0befccb644339379635cae309ae4
Source dataset
uspto-grants-2013_12
Patent number
US08614206B2

Reaction notes

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