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Hydrochloric Acid → n-(2,6-Difluorophenyl)-5-(3-{2-[(5-ethyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(ethyloxy)benzamide

HRID 419600
ノート
印刷プレビュー

反応式

HRID 419600 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]=[CH:19][C:20]([O:34][CH2:35][CH3:36])=[C:21]([CH:33]=2)[C:22]([NH:24][C:25]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=2[F:32])=[O:23])[CH:5]=[CH:4][N:3]=1.[CH2:37]([C:39]1[C:40]([N:48]2[CH2:53][CH2:52][CH:51]([N:54]3[CH2:59][CH2:58][N:57]([S:60]([CH3:63])(=[O:62])=[O:61])[CH2:56][CH2:55]3)[CH2:50][CH2:49]2)=[CH:41][C:42]([O:46][CH3:47])=[C:43]([CH:45]=1)[NH2:44])[CH3:38].Cl>C(O)C(F)(F)F>[F:32][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]([F:31])[C:25]=1[NH:24][C:22](=[O:23])[C:21]1[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:44][C:43]3[CH:45]=[C:39]([CH2:37][CH3:38])[C:40]([N:48]4[CH2:49][CH2:50][CH:51]([N:54]5[CH2:55][CH2:56][N:57]([S:60]([CH3:63])(=[O:62])=[O:61])[CH2:58][CH2:59]5)[CH2:52][CH2:53]4)=[CH:41][C:42]=3[O:46][CH3:47])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH2:35][CH3:36]
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

5

反応物 3

HCID 313Hydrochloric AcidHCID 594529415-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamideHCID 594530035-Ethyl-2-methoxy-4-(4-(4-(methylsulfonyl)piperazin-1-yl)piperidin-1-yl)aniline

生成物 1

HCID 59452680n-(2,6-Difluorophenyl)-5-(3-{2-[(5-ethyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(ethyloxy)benzamide
収率 70.1%

試薬・触媒・溶媒 1

HCID 64092,2,2-Trifluoroethanol溶媒

反応条件

温度
170 °C

実験手順

A mixture of 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide (Intermediate Example 6) (0.125 g, 0.247 mmol), 5-ethyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}aniline (0.098 g, 0.247 mmol) and HCl (4N,1,4-Dioxane, 0.12 mL, 0.494 mmol) in trifluoroethanol (8 mL) was heated at 170° C. for 40 min in the microwave. The reaction was quenched with 7 N NH3 in MeOH and then concentrated to dryness. The residue was then dissolved in DCM and concentrated onto silica gel. Purification by flash column chromatography followed by recrystallization from DCM and EtOH afforded the title compound N-(2,6-difluorophenyl)-5-(3-{2-[(5-ethyl-2-(methyloxy)-4-{4-[4-(methylsulfonyl)-1-piperazinyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(ethyloxy)benzamide (0.150 g, 67%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.76 (s, 1H), 9.30-9.43 (m, 1H), 8.50 (s, 1H), 8.25 (d, J=5.22 Hz, 1H), 8.06 (d, J=2.02 Hz, 1H), 7.74-7.80 (m, 1H), 7.71 (d, J=8.89 Hz, 1H), 7.53 (s, 1H), 7.34-7.49 (m, 2H), 7.28 (d, J=8.43 Hz, 1H), 7.16-7.25 (m, 2H), 6.91-7.00 (m, 1H), 6.83 (s, 1H), 6.58 (d, J=5.04 Hz, 1H), 4.20-4.33 (m, 2H), 3.81 (s, 3H), 3.08-3.16 (m, 4H), 3.00-3.08 (m, 2H), 2.88 (s, 3H), 2.67-2.78 (m, 2H), 2.61-2.66 (m, 4H), 2.56 (q, J=7.51 Hz, 2H), 2.38-2.47 (m, 1H), 1.79-1.92 (m, 2H), 1.52-1.68 (m, 2H), 1.44 (t, J=6.92 Hz, 3H), 1.11 (t, J=7.51 Hz, 3H). MS (M+H, ES+) 866.

後処理

  1. customThe reaction was quenched with 7 N NH3 in MeOH
  2. concentrationconcentrated to dryness
  3. dissolutionThe residue was then dissolved in DCM
  4. concentrationconcentrated onto silica gel
  5. customPurification by flash column chromatography
  6. customfollowed by recrystallization from DCM and EtOH

出典と根拠

ORDレコード
ord-86aa8b9a353b4eec81d124e413390fc6
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…

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