Ammonium Chloride → 2-(4-{2-Amino-4-[(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-5-methoxyphenyl}piperazin-1-yl)-N,N-dimethylacetamide

HRID 1842716

反応式

HRID 1842716 の反応式
[Cl:1][C:2]1[C:3]([C:32]2[CH:33]=[N:34][N:35]3[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=23)=[N:4][C:5]([NH:8][C:9]2[C:14]([O:15][CH3:16])=[CH:13][C:12]([N:17]3[CH2:22][CH2:21][N:20]([CH2:23][C:24]([N:26]([CH3:28])[CH3:27])=[O:25])[CH2:19][CH2:18]3)=[C:11]([N+:29]([O-])=O)[CH:10]=2)=[N:6][CH:7]=1.[NH4+].[Cl-]>C(O)C.O.[Fe]>[NH2:29][C:11]1[CH:10]=[C:9]([NH:8][C:5]2[N:4]=[C:3]([C:32]3[CH:33]=[N:34][N:35]4[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=34)[C:2]([Cl:1])=[CH:7][N:6]=2)[C:14]([O:15][CH3:16])=[CH:13][C:12]=1[N:17]1[CH2:18][CH2:19][N:20]([CH2:23][C:24]([N:26]([CH3:27])[CH3:28])=[O:25])[CH2:21][CH2:22]1

参加物

6

反応物 2

HCID 25517Ammonium ChlorideHCID 712407892-(4-{4-[(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-5-methoxy-2-nitrophenyl}piperazin-1-yl)-N,N-dimethylacetamide2 回

生成物 1

HCID 866773322-(4-{2-Amino-4-[(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-5-methoxyphenyl}piperazin-1-yl)-N,N-dimethylacetamide収率 86.5%

試薬・触媒・溶媒 3

HCID 23925Iron触媒HCID 702Ethanol溶媒HCID 962Water溶媒

実験手順

A mixture of 2-(4-{4-[(5-chloro-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)amino]-5-methoxy-2-nitrophenyl}piperazin-1-yl)-N,N-dimethylacetamide (Intermediate 58, 0.234 g, 0.41 mmol), iron (0.139 g, 2.48 mmol) and NH4Cl (0.015 g, 0.29 mmol) in ethanol (10 mL) and water (3.33 mL) was heated at reflux for 4 h. The mixture was then allowed to cool to r.t., was filtered and the filtrate concentrated in vacuo. Purification by ion exchange chromatography, using an SCX column and eluting with 1M methanolic ammonia, gave a brown gum after concentration of appropriate fractions. Further purification by FCC, eluting with 0-5% CH3OH in CH2Cl2 gave the title compound (0.19 g, 86%) as a yellow foam; 1H NMR: (CDCl3) 2.72 (4H, s), 2.93-3.01 (7H, m), 3.13 (3H, s), 3.27 (2H, s), 3.65-3.83 (2H, m), 3.84 (3H, s), 6.71 (1H, s), 6.96 (1H, td), 7.38 (1H, ddd), 7.55 (1H, s), 7.92 (1H, s), 8.36 (1H, s), 8.57 (1H, dt), 8.61-8.68 (1H, m), 8.94 (1H, s); m/z: ES+ MH+ 536.53.

後処理

  1. temperaturewas heated
  2. temperatureat reflux for 4 h
  3. filtrationwas filtered
  4. concentrationthe filtrate concentrated in vacuo
  5. customPurification by ion exchange chromatography
  6. washeluting with 1M methanolic ammonia
  7. customgave a brown gum after concentration of appropriate fractions
  8. customFurther purification by FCC
  9. washeluting with 0-5% CH3OH in CH2Cl2

出典と根拠

ORDレコード
ord-81994f0781504fa9b59fbe2df706e576
出典データセット
uspto-grants-2015_02
特許番号
US08946235B2

関連ノート

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