4-(4-Fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxylic acid → N-(3-fluoro-4-(3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-4-(4-fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxamide

HRID 2241375Notes

Reaction equation

HRID 2241375 reaction equation
[NH2:1][C:2]1[CH:34]=[CH:33][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[N:13](CC4C=CC(OC)=CC=4)[N:14]=[C:15]([NH:16][CH:17]4[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]4)[C:8]=23)=[C:4]([F:35])[CH:3]=1.[F:36][C:37]1[CH:42]=[CH:41][C:40]([N:43]2[CH:48]=[CH:47][N:46]=[C:45]([C:49](O)=[O:50])[C:44]2=[O:52])=[CH:39][CH:38]=1>>[F:35][C:4]1[CH:3]=[C:2]([NH:1][C:49]([C:45]2[C:44](=[O:52])[N:43]([C:40]3[CH:41]=[CH:42][C:37]([F:36])=[CH:38][CH:39]=3)[CH:48]=[CH:47][N:46]=2)=[O:50])[CH:34]=[CH:33][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[NH:13][N:14]=[C:15]([NH:16][CH:17]3[CH2:22][CH2:21][N:20]([CH3:23])[CH2:19][CH2:18]3)[C:8]=12

Participants

3

Reactant 2

HCID 673494894-(4-Fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxylic acidHCID 685163724-(4-amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-N-(1-methylpiperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine

Product 1

HCID 59304237N-(3-fluoro-4-(3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-4-(4-fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxamideYield 53%

Procedure

Prepared by a 2-step process from 4-(4-amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-N-(1-methylpiperidin-4-yl)-1H-pyrazolo[3,4-b]pyridin-3-amine and 4-(4-fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxylic acid according to the procedure of Example 101, Step B. The crude was rinsed with Et2O to afford 8.8 mg (53%) of the desired product. LRMS (ESI pos) m/e 573.0 (M+1). 1H NMR (400 MHz, CD3OD/CDCl3) δ 8.14 (d, 1H), 8.05 (dd, 1H), 7.86 (m, 2H), 7.57 (m, 2H), 7.51 (d, 1H), 7.34 (m, 3H), 6.12 (d, 1H), 3.71 (m, 1H), 2.92 (m, 2H), 2.35 (s, 3H), 2.29 (m, 2H), 2.22 (m, 2H), 1.65 (m, 2H); 19F NMR (376 MHz, CD3OD/CDCl3) δ −112.1, −129.4.

Workup

  1. washThe crude was rinsed with Et2O

Sources & evidence

ORD record
ord-619458ab55794c06939d7aec68f6bae1
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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