4-Fluoroaniline → N-(3-fluoro-4-(2-(3-(4-methylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

HRID 1676291Notes

Reaction equation

HRID 1676291 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([NH2:28])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]#[C:19][CH2:20][N:21]3[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]3)[S:17][C:10]=12.[F:29][C:30]1[CH:35]=[CH:34][C:33]([N:36]2[CH:41]=[CH:40][CH:39]=[C:38]([C:42](O)=[O:43])[C:37]2=[O:45])=[CH:32][CH:31]=1.O=C1C(C(OC)=O)=CC=CO1.FC1C=CC(N)=CC=1>>[F:1][C:2]1[CH:3]=[C:4]([NH:28][C:42]([C:38]2[C:37](=[O:45])[N:36]([C:33]3[CH:32]=[CH:31][C:30]([F:29])=[CH:35][CH:34]=3)[CH:41]=[CH:40][CH:39]=2)=[O:43])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[C:16]([C:18]#[C:19][CH2:20][N:21]3[CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]3)[S:17][C:10]=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 673454993-Fluoro-4-(2-(3-(4-methylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)aniline

Product 1

HCID 58949508N-(3-fluoro-4-(2-(3-(4-methylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamideYield 19%

Procedure

The title compound was prepared from 3-fluoro-4-(2-(3-(4-methylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)aniline (Example 17, Step B) 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 2005/0239820) according to the procedure for Example 89. The crude was purified by silica gel flash column chromatography (5% MeOH in CH2Cl2) to afford 3 mg (19%) of the desired product. 1H NMR (400 MHz, CD3OD/CDCl3) δ 8.73 (dd, 1H), 8.45 (d, 1H), 7.98 (dd, 1H), 7.84 (dd, 1H), 7.58 (s, 1H), 7.48 (m, 2H), 7.40 (d, 1H), 7.31 (t, 2H), 6.74 (t, 1H), 6.63 (d, 1H), 3.64 (s, 2H), 2.60-2.76 (m, 8H), 2.33 (s, 3H); 19F NMR (376 MHz, CD3OD/CDCl3) δ −112.1, −127.6. LRMS (ESI pos) m/e 612.1 (M+1).

Workup

  1. customfollowed by hydrolysis
  2. customThe crude was purified by silica gel flash column chromatography (5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-8e6a422e2db24d8ab653cc12a48bd6e1
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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