2-Fluoro-5-methylbenzeneboronic acid → 5-Amino-N-(1-(2,2-difluoroethyl)-5-(4-hydroxyazepan-1-yl)-1H-pyrazol-4-yl)-2-(2-fluoro-5-methylphenyl)thiazole-4-carboxamide

HRID 1915847Notes

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]([CH3:42])=[CH:38][C:37]=1B(O)O>>[NH2:27][C:4]1[S:3][C:2]([C:37]2[CH:38]=[C:39]([CH3:42])[CH:40]=[CH:41][C:36]=2[F:35])=[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

Reactant 2

HCID 103518842-Fluoro-5-methylbenzeneboronic acid

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

Product 1

HCID 715399655-Amino-N-(1-(2,2-difluoroethyl)-5-(4-hydroxyazepan-1-yl)-1H-pyrazol-4-yl)-2-(2-fluoro-5-methylphenyl)thiazole-4-carboxamideYield 50%

Procedure

Following the procedure for Example 105 starting with tert-butyl 2-bromo-4-(1-(2,2-difluoroethyl)-5-(4-hydroxyazepan-1-yl)-1H-pyrazol-4-ylcarbamoyl)thiazol-5-ylcarbamate (0.13 g, 0.23 mmol) and 2-fluoro-5-methylbenzeneboronic acid (53 mg, 0.35 mmol) gave 111 as a black solid (56 mg, 50% over two steps). 1H NMR (400 MHz, d6-DMSO) δ 8.93 (s, 1H), 8.08 (d, J=7.4 Hz, 1H), 7.66 (s, 1H), 7.42 (s, 2H), 7.24 (d, J=8.7 Hz, 2H), 6.39 (tt, J=55.3, 4.2 Hz, 1H), 4.55 (d, J=3.8 Hz, 1H), 4.42 (td, J=14.5, 4.2 Hz, 2H), 3.86-3.80 (m, 1H), 3.29-3.03 (m, 4H), 2.37 (s, 3H), 1.94-1.84 (m, 3H), 1.77-1.55 (m, 3H). LCMS (ES+) m/z 495 (M+1).

Sources & evidence

ORD record: ord-997eac3c94ed43f982ea125b9174df23
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08614206B2

Reaction notes

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