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

HRID 2241362Notes

Reaction equation

HRID 2241362 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][CH:46]=[C:45]([C:49](O)=[O:50])[C:44]2=[O:52])=[CH:39][CH:38]=1.O=C1C(C(OC)=O)=CC=CO1.FC1C=CC(N)=CC=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:39]=[CH:38][C:37]([F:36])=[CH:42][CH:41]=3)[CH:48]=[CH:47][CH: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[CH2:18][CH2:19][N:20]([CH3:23])[CH2:21][CH2:22]3)[C:8]=12

Participants

5

Reactant 4

HCID 97314-FluoroanilineHCID 117704Methyl 2-oxo-2H-pyran-3-carboxylateHCID 210815271-(4-Fluorophenyl)-2-oxo-1,2-dihydropyridine-3-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 59304302N-(3-fluoro-4-(3-(1-methylpiperidin-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-4-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamideYield 73%

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 (prepared in Example 101, step A) and 1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxylic acid (prepared from methyl 2-oxo-2H-pyran-3-carboxylate with 4-fluoroaniline and followed by hydrolysis using the methods described in US Publication No. 2005/0239820) according to the procedure of Example 101. The crude was rinsed with Et2O to afford 14 mg (73%) of the desired product. LRMS (ESI pos) m/e 572.0 (M+1). 1H-NMR (400 MHz, CD3OD/CDCl3) δ 8.72 (d, 1H), 8.24 (d, 1H), 8.02 (dd, 1H), 8.02 (dd, 1H), 7.87 (d, 1H), 7.47 (m, 2H), 7.41 (m, 1H), 7.38 (m, 3H), 6.72 (m, 1H), 6.12 (d, 1H), 3.70 (m, 1H), 2.88 (d, 2H), 2.35 (s, 3H), 2.24 (m, 1H), 2.21 (m, 2H), 1.62 (m, 2H); 19F NMR (376 MHz, CD3OD/CDCl3) δ −112.6, −128.0.

Workup

  1. customfollowed by hydrolysis
  2. washThe crude was rinsed with Et2O

Sources & evidence

ORD record
ord-fc2a994ca67c45ab98072f6479c24ebd
Source dataset
uspto-grants-2010_05
Patent number
US07723330B2

Reaction notes

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