5-Cyano-2-fluorobenzeneboronic acid → 5-amino-N-(5-(4-(aminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(5-cyano-2-fluorophenyl)thiazole-4-carboxamide

HRID 2089412Notes

Reaction equation

C(OC([NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][N:13]([C:16]2[N:20]([CH3:21])[N:19]=[CH:18][C:17]=2[NH:22][C:23]([C:25]2[N:26]=[C:27](Br)[S:28][C:29]=2[NH:30]C(=O)OC(C)(C)C)=[O:24])[CH2:12][CH2:11]1)=O)CCC.[C:39]([C:41]1[CH:42]=[CH:43][C:44]([F:50])=[C:45](B(O)O)[CH:46]=1)#[N:40]>>[NH2:30][C:29]1[S:28][C:27]([C:43]2[CH:42]=[C:41]([C:39]#[N:40])[CH:46]=[CH:45][C:44]=2[F:50])=[N:26][C:25]=1[C:23]([NH:22][C:17]1[CH:18]=[N:19][N:20]([CH3:21])[C:16]=1[N:13]1[CH2:14][CH2:15][CH:10]([CH2:9][NH2:8])[CH2:11][CH2:12]1)=[O:24]

Participants

Reactant 2

HCID 27833615-Cyano-2-fluorobenzeneboronic acid

HCID 58464898tert-butyl 4-(5-(4-(butyloxycarbonylaminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-bromothiazol-5-ylcarbamate

Product 1

HCID 584647825-amino-N-(5-(4-(aminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(5-cyano-2-fluorophenyl)thiazole-4-carboxamideYield 35%

Procedure

Following Example 278, Suzuki coupling of tert-butyl 4-(5-(4-(butyloxycarbonylaminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-bromothiazol-5-ylcarbamate and 5-cyano-2-fluorophenylboronic acid gave 298 as a yellow solid (32 mg, 35% over two steps). 1H NMR (400 MHz, d4-MeOD) 8.75 (dd, J=6.9, 2.2 Hz, 1H), 7.80-7.75 (m, 1H), 7.51-7.45 (m, 2H), 3.74 (s, 3H), 3.25-3.11 (m, 4H), 2.60 (d, J=6.6 Hz, 2H), 1.87 (d, J=12.5 Hz, 2H), 1.53-1.49 (m, 1H), 1.43-1.32 (m, 2H). LCMS (ES+) m/z 455 (M+1)

Sources & evidence

ORD record: ord-8ff8fe0beb6749a3972cc3ff114ca825
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08436001B2

Reaction notes

Loading…