(4-(7-(4-Amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)phenyl)(morpholino)methanone → N-(3-fluoro-4-(2-(4-(morpholine-4-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-4-(4-fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxamide

HRID 1676402Notes

Reaction equation

HRID 1676402 reaction equation
[NH2:1][C:2]1[CH:31]=[CH:30][C:5]([O:6][C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[CH:13]=[C:14]([C:16]4[CH:21]=[CH:20][C:19]([C:22]([N:24]5[CH2:29][CH2:28][O:27][CH2:26][CH2:25]5)=[O:23])=[CH:18][CH:17]=4)[S:15][C:8]=23)=[C:4]([F:32])[CH:3]=1.[F:33][C:34]1[CH:39]=[CH:38][C:37]([N:40]2[CH:45]=[CH:44][N:43]=[C:42]([C:46](O)=[O:47])[C:41]2=[O:49])=[CH:36][CH:35]=1>>[F:32][C:4]1[CH:3]=[C:2]([NH:1][C:46]([C:42]2[C:41](=[O:49])[N:40]([C:37]3[CH:38]=[CH:39][C:34]([F:33])=[CH:35][CH:36]=3)[CH:45]=[CH:44][N:43]=2)=[O:47])[CH:31]=[CH:30][C:5]=1[O:6][C:7]1[CH:12]=[CH:11][N:10]=[C:9]2[CH:13]=[C:14]([C:16]3[CH:17]=[CH:18][C:19]([C:22]([N:24]4[CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)=[O:23])=[CH:20][CH:21]=3)[S:15][C:8]=12

Participants

3

Reactant 2

HCID 67347265(4-(7-(4-Amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)phenyl)(morpholino)methanoneHCID 673494894-(4-Fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxylic acid

Product 1

HCID 58949529N-(3-fluoro-4-(2-(4-(morpholine-4-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-4-(4-fluorophenyl)-3-oxo-3,4-dihydropyrazine-2-carboxamideYield 72%

Procedure

Prepared from (4-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)phenyl)(morpholino)methanone (Example 129, Step A) and 4-(4-fluorophenyl)-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 (3 to 5% MeOH in CH2Cl2) to afford 47 mg (72%) of the desired product. LRMS (APCI pos) m/e 666.2 (M+1). 1H-NMR (400 MHz, CDCl3/CD3OD) δ 8.47 (d, 1H), 8.06 (dd, 1H), 7.93 (d, 2H), 7.90 (d, 1H), 7.87 (s, 1H), 7.82 (d, 1H), 7.59 (m, 4H), 7.52 (d, 1H), 7.40 (t, 1H), 7.34 (m, 3H), 6.67 (d, 1H), 3.69-3.79 (m, 8H); 19F NMR (376 MHz, CDCl3/CD3OD) δ −112.7, −128.7.

Workup

  1. customThe crude was purified by silica gel flash column chromatography (3 to 5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-d5b7acf704204c49800fa919df228c7f
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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