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

HRID 419377
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HRID 419377 반응식
Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]3=[N:10][C:9]=2[C:17]2[CH:18]=[C:19]([CH:31]=[CH:32][CH:33]=2)[C:20]([NH:22][C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=2[F:30])=[O:21])[CH:5]=[CH:4][N:3]=1.[NH2:34][C:35]1[CH:40]=[CH:39][C:38]([N:41]2[CH2:46][CH2:45][CH:44]([N:47]([CH3:49])[CH3:48])[CH2:43][CH2:42]2)=[CH:37][C:36]=1[O:50][CH3:51].C1(C)C=CC(S(O)(=O)=O)=CC=1>CC(O)C.C(Cl)Cl>[F:30][C:24]1[CH:25]=[CH:26][CH:27]=[C:28]([F:29])[C:23]=1[NH:22][C:20](=[O:21])[C:19]1[CH:31]=[CH:32][CH:33]=[C:17]([C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]3[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:34][C:35]3[CH:40]=[CH:39][C:38]([N:41]4[CH2:46][CH2:45][CH:44]([N:47]([CH3:48])[CH3:49])[CH2:43][CH2:42]4)=[CH:37][C:36]=3[O:50][CH3:51])[N:7]=2)[CH:18]=1
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참가 물질

6

반응물 3

HCID 6101p-Toluenesulfonic acidHCID 574161531-(4-amino-3-methoxyphenyl)-N,N-dimethylpiperidin-4-amineHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

생성물 1

HCID 59452719N-(2,6-difluorophenyl)-3-[3-(2-{[4-[4-(dimethylamino)-1-piperidinyl]-2-(methyl-oxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]benzamide수율 77.9%

시약·촉매·용매 2

HCID 3776Isopropanol용매HCID 6344Dichloromethane용매

실험 절차

3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (140 mg, 0.30 mmol), 1-[4-amino-3-(methyloxy)phenyl]-N,N-dimethyl-4-piperidinamine (67 mg, 0.27 mmol) and p-toluenesulfonic acid (140 mg, 0.71 mmol) in iPrOH was heated in the microwave at 180° C. for 13.5 min. The mixture was dissolved in DCM and concentrated onto silica gel. The crude material was purified by flash column chromatography to give the title compound (142 mg, 70%). 1H NMR (400 MHz, DMSO-d6) δ 10.23 (s, 1H), 9.40 (s, 1H), 8.45 (s, 1H), 8.33 (s, 1H), 8.20 (d, J=5.2 Hz, 1H), 8.05 (d, J=8.0 Hz, 1H), 7.81 (d, J=7.6 Hz, 1H), 7.72 (d, J=8.8 Hz, 1H), 7.60 (t, J=7.6 Hz, 1H), 7.48-7.36 (m, 3H), 7.20 (t, J=8.2 Hz, 2H), 6.97 (t, J=6.8 Hz, 1H), 6.67 (m, 1H), 6.49-6.45 (m, 2H), 3.79 (s, 3H), 3.70 (d, J=12.4 Hz, 2H), 2.68-2.63 (m, 2H), 2.18 (s, 7H), 1.84-1.81 (m, 2H), 1.52-1.44 (m, 2H). MS (ESI) m/z=675 [M+H]+.

후처리

  1. concentrationconcentrated onto silica gel
  2. customThe crude material was purified by flash column chromatography

출처 및 근거

ORD 기록
ord-d9b7fda21d9f4b00b242b7c576fc2a57
출처 데이터셋
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08093239B2

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