4-(Cyclopropylmethyl)-3-oxo-3,4-dihydropyrazine-2-carboxylic acid → 4-(cyclopropylmethyl)-N-(3-fluoro-4-(2-(4-(methylcarbamoyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-3-oxo-3,4-dihydropyrazine-2-carboxamide

HRID 1676343Notes

Reaction equation

HRID 1676343 reaction equation
[NH2:1][C:2]1[CH:27]=[CH:26][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[CH:25]=[CH:24][C:19]([C:20]([NH:22][CH3:23])=[O:21])=[CH:18][CH:17]=4)[S:15][C:8]=23)=[C:4]([F:28])[CH:3]=1.[CH:29]1([CH2:32][N:33]2[CH:38]=[CH:37][N:36]=[C:35]([C:39](O)=[O:40])[C:34]2=[O:42])[CH2:31][CH2:30]1>>[CH:29]1([CH2:32][N:33]2[CH:38]=[CH:37][N:36]=[C:35]([C:39]([NH:1][C:2]3[CH:27]=[CH:26][C:5]([O:6][C:7]4[CH:12]=[CH:11][N:10]=[C:9]5[CH:13]=[C:14]([C:16]6[CH:25]=[CH:24][C:19]([C:20](=[O:21])[NH:22][CH3:23])=[CH:18][CH:17]=6)[S:15][C:8]=45)=[C:4]([F:28])[CH:3]=3)=[O:40])[C:34]2=[O:42])[CH2:30][CH2:31]1

Participants

3

Reactant 2

HCID 673454214-(Cyclopropylmethyl)-3-oxo-3,4-dihydropyrazine-2-carboxylic acidHCID 673486984-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-N-methylbenzamide

Product 1

HCID 589495174-(cyclopropylmethyl)-N-(3-fluoro-4-(2-(4-(methylcarbamoyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-3-oxo-3,4-dihydropyrazine-2-carboxamideYield 22%

Procedure

Prepared from 4-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)-N-methylbenzamide (Example 95, Step A) and 4-(cyclopropylmethyl)-3-oxo-3,4-dihydropyrazine-2-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 8 mg (22%) of the desired product. LRMS (ESI pos) m/e 570.2 (M+1). 1H NMR (400 MHz, CDCl3/CD3OD) δ 8.47 (d, 1H), 8.08 (dd, 1H), 8.03 (d, 1H), 7.93 (q, 4H), 7.79 (d, 1H), 7.76 (s, 1H), 7.55 (m, 1H), 7.40 (t, 1H), 6.67 (d, 1H), 4.02 (d, 2H), 2.97 (s, 3H), 1.41 (m, 1H), 0.69 (m, 2H), 0.52 (m, 2H); 19F NMR (376 MHz, CDCl3/CD3OD) δ −128.6.

Workup

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

Sources & evidence

ORD record
ord-9e1dc37366214cd286683915cdd61a32
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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