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

반응식

HRID 1842716 반응식
[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

참가 물질

6

반응물 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-dimethylacetamide2회

생성물 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-dimethylacetamide수율 86.5%

시약·촉매·용매 3

HCID 23925Iron촉매HCID 702Ethanol용매HCID 962Water용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-81994f0781504fa9b59fbe2df706e576
출처 데이터셋
uspto-grants-2015_02
특허 번호
US08946235B2

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