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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 419318
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HRID 419318 반응식
[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
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참가 물질

4

반응물 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

생성물 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]benzamide수율 40.6%

시약·촉매·용매 1

HCID 8028
Tetrahydrofuran
용매

실험 절차

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.

후처리

  1. customPurification by flash chromatography

출처 및 근거

ORD 기록
ord-ddb5f7c0249f412895a27e0f614ad686
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08093239B2

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