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

HRID 419499
ノート
印刷プレビュー

反応式

HRID 419499 の反応式
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.[CH2:34]([O:36][C:37]1[CH:43]=[C:42]([CH2:44][CH2:45][N:46]2[CH2:51][CH2:50][N:49]([CH3:52])[CH2:48][CH2:47]2)[CH:41]=[CH:40][C:38]=1[NH2:39])[CH3:35].C1(C)C=CC(S(O)(=O)=O)=CC=1.C[O-].[Na+]>C(Cl)Cl.CC(O)C>[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:39][C:38]3[CH:40]=[CH:41][C:42]([CH2:44][CH2:45][N:46]4[CH2:47][CH2:48][N:49]([CH3:52])[CH2:50][CH2:51]4)=[CH:43][C:37]=3[O:36][CH2:34][CH3:35])[N:7]=2)[CH:18]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 4

HCID 6101p-Toluenesulfonic acidHCID 10942334Sodium MethoxideHCID 594528212-(Ethyloxy)-4-[2-(4-methyl-1-piperazinyl)ethyl]anilineHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

生成物 1

HCID 59452973N-(2,6-difluorophenyl)-3-{3-[2-({2-(ethyloxy)-4-[2-(4-methyl-1-piperazinyl)ethyl]-phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamide
収率 56%

試薬・触媒・溶媒 2

HCID 3776Isopropanol溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
130 °C

実験手順

3-[3-(2-Chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (100 mg, 0.22 mmol), 2-(ethyloxy)-4-[2-(4-methyl-1-piperazinyl)ethyl]aniline (Example 146, step D) (46 mg, 0.17 mmol), and p-toluenesulfonic acid (99 mg, 0.52 mmol) were weighed into a 20 mL vial. 7 mL of iPrOH was added and the mixture was heated to 130° C. for 72 h. The mixture was transferred to a 50 mL round bottom and neutralized with 2 mL of 0.5 N sodium methoxide. The solvent was rotovaped down. The residue was taken up in 10 mL of DCM. 1 g of silica gel was added. The solvent was rotovaped down and the pre-adsorbed solids were purified by flash chromatography to give the title compound (67 mg, 0.09 mmol, 56%); 1H NMR (400 MHz, DMSO-d6) δ ppm 10.21 (s, 1H), 9.34 (s, 1H), 8.40 (s, 1H), 8.34 (s, 1H), 8.27 (s, 1H), 8.02 (s, 1H), 7.80 (s, 1H), 7.73 (s, 1H), 7.65 (s, 1H), 7.59 (s, 1H), 7.46 (s, 1H), 7.38 (s, 1H), 7.18 (s, 2H), 6.96 (s, 2H), 6.72 (s, 1H), 6.46 (s, 1H), 4.02-4.11 (m, 2H), 2.60-2.71 (m, 2H), 2.25-2.32 (m, 10H), 2.12 (s, 3H), 1.26 (s, 3H). MS (ESI): 689 [M+H]+.

後処理

  1. addition1 g of silica gel was added
  2. customthe pre-adsorbed solids were purified by flash chromatography

出典と根拠

ORDレコード
ord-31269d6f804e4233ab0f6bbdce39b79f
出典データセット
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08093239B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート