4-Methoxy-2-(trifluoromethyl)phenylboronic acid → 5-amino-N-(5-(4-(aminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(4-methoxy-2-(trifluoromethyl)phenyl)thiazole-4-carboxamide

HRID 2089396Notes

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.[CH3:39][O:40][C:41]1[CH:46]=[CH:45][C:44](B(O)O)=[C:43]([C:50]([F:53])([F:52])[F:51])[CH:42]=1>>[NH2:30][C:29]1[S:28][C:27]([C:44]2[CH:45]=[CH:46][C:41]([O:40][CH3:39])=[CH:42][C:43]=2[C:50]([F:51])([F:52])[F:53])=[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 121094604-Methoxy-2-(trifluoromethyl)phenylboronic acid

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

Product 1

HCID 584650515-amino-N-(5-(4-(aminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-yl)-2-(4-methoxy-2-(trifluoromethyl)phenyl)thiazole-4-carboxamideYield 54%

Procedure

Following the procedure for Example 337 starting with tert-butyl 4-(5-(4-(butyloxycarbonylaminomethyl)piperidin-1-yl)-1-methyl-1H-pyrazol-4-ylcarbamoyl)-2-bromothiazol-5-ylcarbamate and 4-methoxy-2-(trifluoromethyl)benzeneboronic acid gave 280 as a brown solid (56 mg, 54%). 1H NMR (400 MHz, d4-MeOD) δ 7.65 (d, J=8.6 Hz, 1H), 7.58 (s, 1H), 7.37 (d, J=2.6 Hz, 1H), 7.27 (dd, J=8.6, 2.6 Hz, 1H), 3.94 (s, 3H), 3.72 (s, 3H), 3.19-3.06 (m, 4H), 2.62 (d, J=6.5 Hz, 2H), 1.84 (d, J=12.5 Hz, 2H), 1.57-1.46 (m, 1H), 1.37 (qd, J=11.7, 4.9 Hz, 2H). LCMS (ES+) m/z 510 (M+1).

Sources & evidence

ORD record: ord-74f9033d8b6c49948fff81c9c545084f
Source dataset: uspto-grants-2013_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08436001B2

Reaction notes

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