Methyl iodide → N-(3-fluoro-4-(2-(4-(morpholine-4-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-4-methyl-3-oxo-3,4-dihydropyrazine-2-carboxamide

HRID 1676360Notes

Reaction equation

HRID 1676360 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.[CH3:33][N:34]1[CH:39]=[CH:38][N:37]=[C:36]([C:40](O)=[O:41])[C:35]1=[O:43].O=C1NC=CN=C1C(OC)=O.IC>>[F:32][C:4]1[CH:3]=[C:2]([NH:1][C:40]([C:36]2[C:35](=[O:43])[N:34]([CH3:33])[CH:39]=[CH:38][N:37]=2)=[O:41])[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

5

Reactant 4

HCID 6328Methyl iodideHCID 1514283Methyl 3-hydroxypyrazine-2-carboxylateHCID 673467654-Methyl-3-oxo-3,4-dihydropyrazine-2-carboxylic acidHCID 67347265(4-(7-(4-Amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)phenyl)(morpholino)methanone

Product 1

HCID 58949472N-(3-fluoro-4-(2-(4-(morpholine-4-carbonyl)phenyl)thieno[3,2-b]pyridin-7-yloxy)phenyl)-4-methyl-3-oxo-3,4-dihydropyrazine-2-carboxamideYield 25%

Procedure

Prepared from (4-(7-(4-amino-2-fluorophenoxy)thieno[3,2-b]pyridin-2-yl)phenyl)(morpholino)methanone (prepared as in Example 129, Step A) and 4-methyl-3-oxo-3,4-dihydropyrazine-2-carboxylic acid (prepared from methyl 3-oxo-3,4-dihydropyrazine-2-carboxylate with iodomethane and followed by hydrolysis using the methods described in Example 149, Steps A and B) according to the procedure of Example 89. The crude was purified by silica gel flash column chromatography (5% MeOH in CH2Cl2) to afford 6.6 mg (25%) of the desired product. LRMS (APCI pos) m/e 586.2 (M+1). 1H-NMR (400 MHz, CDCl3/CD3OD) δ 8.47 (d, 1H), 8.07 (dd, 1H), 7.92 (m, 3H), 7.86 (s, 1H), 7.76 (d, 1H), 7.55 (m, 3H), 7.39 (t, 1H), 6.67 (d, 1H), 3.75 (s, 3H), 3.55-3.80 (m, 8H); 19F NMR (376 MHz, CDCl3/CD3OD) δ −128.3.

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-1b8bc19be9404156b273a9e189a0392d
Source dataset
uspto-grants-2011_08
Patent number
US08003662B2

Reaction notes

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