Methyl vinyl sulfone → N-(2,6-difluorophenyl)-3-[3-(2-{[2-methyl-4-({1-[2-(methylsulfonyl)ethyl]-4-piperidinyl}oxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzamide

HRID 419318Notes

Reaction equation

HRID 419318 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10](=[O:47])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[N:18]=[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]3[C:25]=2[C:26]2[CH:31]=[CH:30][N:29]=[C:28]([NH:32][C:33]3[CH:38]=[CH:37][C:36]([O:39][CH:40]4[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]4)=[CH:35][C:34]=3[CH3:46])[N:27]=2)[CH:12]=1.[CH:48]([S:50]([CH3:53])(=[O:52])=[O:51])=[CH2:49]>C1COCC1>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[NH:9][C:10](=[O:47])[C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([C:17]2[N:18]=[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]3[C:25]=2[C:26]2[CH:31]=[CH:30][N:29]=[C:28]([NH:32][C:33]3[CH:38]=[CH:37][C:36]([O:39][CH:40]4[CH2:45][CH2:44][N:43]([CH2:49][CH2:48][S:50]([CH3:53])(=[O:52])=[O:51])[CH2:42][CH2:41]4)=[CH:35][C:34]=3[CH3:46])[N:27]=2)[CH:12]=1

Participants

4

Reactant 2

HCID 19354Methyl vinyl sulfoneHCID 59452825N-(2,6-difluorophenyl)-3-[3-(2-{[2-methyl-4-(4-piperidinyloxy)phenyl]-amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzamide

Product 1

HCID 59452726N-(2,6-difluorophenyl)-3-[3-(2-{[2-methyl-4-({1-[2-(methylsulfonyl)ethyl]-4-piperidinyl}oxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzamideYield 40.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To N-(2,6-difluorophenyl)-3-[3-(2-{[2-methyl-4-(4-piperidinyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzamide (Example 6) (0.10 g, 0.16 mmol) in THF (5 mL) was added methyl vinyl sulfone (0.028 mL, 0.32 mmol) in one portion. The reaction was stirred at rt until complete by MS. Purification by flash chromatography provided the title compound (0.048 g, 0.065 mmol, 40%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.58-1.66 (m, 2H), 1.89-1.97 (m, 2H), 2.19 (s, 3H), 2.22-2.33 (m, 2H), 2.68-2.77 (m, 4H), 3.02 (s, 3H), 3.23-3.28 (m, 2H), 4.34-4.39 (m, 1H), 6.45 (d, J=4.9 Hz, 1H), 6.76-6.85 (m, 1H), 6.88 (s, 2H), 7.22 (dt, J=16.3, 8.2 Hz, 3H), 7.36-7.48 (m, 2H), 7.62 (t, J=7.6 Hz, 1H), 7.71 (d, J=8.8 Hz, 1H), 7.78-7.89 (m, 1H), 8.06 (d, J=7.3 Hz, 1H), 8.18 (d, J=5.1 Hz, 1H), 8.31 (s, 1H), 8.89 (s, 1H), 9.30-9.36 (m, 1H), 10.24 (s, 1H). MS (M+H, ES+) 738.

Workup

  1. customPurification by flash chromatography

Sources & evidence

ORD record
ord-ddb5f7c0249f412895a27e0f614ad686
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

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