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

Reaktionsgleichung

Reaktionsgleichung von HRID 1842716
[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

Komponenten

6

Edukt 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×

Produkt 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-dimethylacetamideAusbeute 86,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23925IronKatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-81994f0781504fa9b59fbe2df706e576
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946235B2

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