3-Cyanophenylboronic acid → 5-amino-N-(5-(4-(aminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(3-cyanophenyl)thiazole-4-carboxamide

HRID 1185327Notes

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]=[C:43](B(O)O)[CH:44]=[CH:45][CH:46]=1)#[N:40]>>[NH2:30][C:29]1[S:28][C:27]([C:45]2[CH:44]=[CH:43][CH:42]=[C:41]([C:39]#[N:40])[CH:46]=2)=[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 27343253-Cyanophenylboronic acid

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

Product 1

HCID 584648145-amino-N-(5-(4-(aminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(3-cyanophenyl)thiazole-4-carboxamideYield 42%

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 3-cyanophenyl boronic acid gave 250 as a pale brown solid (36 mg, 42% over two steps). 1H NMR (400 MHz, d6-DMSO) δ 9.09 (s, 1H), 8.42 (s, 1H), 8.11 (d, J=7.9 Hz, 1H), 7.86 (d, J=7.9 Hz, 1H), 7.68 (t, J=7.9 Hz, 1H), 7.56 (s, 2H), 7.33 (s, 1H), 3.66 (s, 3H), 3.16-2.99 (m, 4H), 2.47 (d, J=5.7 Hz, 2H), 1.82-1.73 (m, 4H), 1.30-1.17 (m, 3H). LCMS (ES+) m/z 437 (M+1)

Sources & evidence

ORD record: ord-22dd07064daa4c7294180888a17dba3d
Source dataset: uspto-grants-2014_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08669361B2

Reaction notes

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