1-Benzyl-5-chloro-2-oxo-1,2-dihydro-3-pyridinecarboxylic acid → 1-benzyl-5-chloro-N-(3-fluoro-4-(2-(3-(4-methylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

HRID 1676311Notes

Reaction equation

HRID 1676311 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.[CH2:29]([N:36]1[CH:41]=[C:40]([Cl:42])[CH:39]=[C:38]([C:43](O)=[O:44])[C:37]1=[O:46])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>>[CH2:29]([N:36]1[CH:41]=[C:40]([Cl:42])[CH:39]=[C:38]([C:43]([NH:28][C:4]2[CH:5]=[CH:6][C:7]([O:8][C:9]3[CH:14]=[CH:13][N:12]=[C:11]4[CH:15]=[C:16]([C:18]#[C:19][CH2:20][N:21]5[CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]5)[S:17][C:10]=34)=[C:2]([F:1])[CH:3]=2)=[O:44])[C:37]1=[O:46])[C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1

Participants

3

Reactant 2

HCID 27643521-Benzyl-5-chloro-2-oxo-1,2-dihydro-3-pyridinecarboxylic acidHCID 673454993-Fluoro-4-(2-(3-(4-methylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)aniline

Product 1

HCID 589494471-benzyl-5-chloro-N-(3-fluoro-4-(2-(3-(4-methylpiperazin-1-yl)prop-1-ynyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-2-oxo-1,2-dihydropyridine-3-carboxamideYield 52%

Procedure

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-benzyl-5-chloro 2-oxo-1,2-dihydropyridine-3-carboxylic acid according to the procedure of Example 89. The crude was purified by silica gel flash column chromatography (5% MeOH in CH2Cl2) to afford 16.7 mg (52%) of the desired product. LRMS (APCI pos) m/e 642.1, 644.1 (M+1, Cl pattern). 1H-NMR (400 MHz, CD3OD) δ 8.50 (t, 2H), 8.29 (d, 1H), 8.02 (dd, 1H), 7.59 (s, 1H), 7.33-7.48 (m, 7H), 6.71 (d, 1H), 5.32 (s, 2H), 3.67 (s, 2H), 2.56-2.74 (m, 8H), 2.30 (s, 3H); 19F NMR (376 MHz, CD3OD) δ −129.7.

Workup

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

Sources & evidence

ORD record
ord-f44fec6f1ea047ad9ea009a755a3445f
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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