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Acetic Acid → N-(2,6-difluorophenyl)-3-{3-[2-({2-methyl-4-[(1-methyl-4-piperidinyl)oxy]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamide

HRID 419317
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HRID 419317 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.[C:48](O)(=O)C.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CO>[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]([CH3:48])[CH2:42][CH2:41]4)=[CH:35][C:34]=3[CH3:46])[N:27]=2)[CH:12]=1
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 712FormaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 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 59452904N-(2,6-difluorophenyl)-3-{3-[2-({2-methyl-4-[(1-methyl-4-piperidinyl)oxy]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamide
수율 43.7%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

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) (0.098 g, 0.16 mmol) in DCM (4 mL) and MeOH (2 mL) was added acetic acid (0.20 mL, 1M in DCM, 0.20 mmol) and formaldehyde (0.024 mL, 37% weight in H2O, 0.32 mmol). Sodium triacetoxyborohydride (0.053 g, 0.25 mmol) in one portion and the reaction was stirred at rt until complete by MS. Purification by flash chromatography, followed by preparative HPLC chromatography (prep-HPLC) provided the title compound (0.044 g, 0.070 mmol, 43%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.58-1.67 (m, 2H), 1.88-1.95 (m, 2H), 2.11-2.21 (m, 8H), 2.55-2.65 (m, 2H), 4.33 (s, 1H), 6.45 (d, J=5.1 Hz, 1H), 6.81 (d, J=8.1 Hz, 2H), 6.87 (s, 2H), 7.17-7.26 (m, 3H), 7.36-7.47 (m, 2H), 7.62 (t, J=7.8 Hz, 1H), 7.71 (d, J=9.1 Hz, 1H), 7.77-7.85 (m, 1H), 8.06 (d, J=9.5 Hz, 1H), 8.18 (d, J=5.3 Hz, 1H), 8.31 (s, 1H), 8.89 (s, 1H), 9.32 (br. s., 1H). MS (M+H, ES+) 646.

후처리

  1. customPurification by flash chromatography

출처 및 근거

ORD 기록
ord-4607b0e2e9694e26884e1b6e01194396
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08093239B2

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