Ammonium Chloride → N-[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]-4-(3-dimethylaminoazetidin-1-yl)-6-methoxybenzene-1,3-diamine

HRID 1842772

Reaktionsgleichung

Reaktionsgleichung von HRID 1842772
[Cl:1][C:2]1[C:3]([C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[NH:29][CH:28]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[C:13]([N+:15]([O-])=O)[C:12]([N:18]3[CH2:21][CH:20]([N:22]([CH3:24])[CH3:23])[CH2:19]3)=[CH:11][C:10]=2[O:25][CH3:26])=[N:6][CH:7]=1.[NH4+].[Cl-]>C(O)C.O.[Fe]>[Cl:1][C:2]1[C:3]([C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[NH:29][CH:28]=2)=[N:4][C:5]([NH:8][C:9]2[C:10]([O:25][CH3:26])=[CH:11][C:12]([N:18]3[CH2:21][CH:20]([N:22]([CH3:24])[CH3:23])[CH2:19]3)=[C:13]([NH2:15])[CH:14]=2)=[N:6][CH:7]=1

Komponenten

6

Edukt 2

HCID 25517Ammonium ChlorideHCID 712408905-chloro-N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-(1H-indol-3-yl)pyrimidin-2-amine2×

Produkt 1

HCID 86677283N-[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]-4-(3-dimethylaminoazetidin-1-yl)-6-methoxybenzene-1,3-diamineAusbeute 99,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23925IronKatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

A mixture of 5-chloro-N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-(1H-indol-3-yl)pyrimidin-2-amine (Intermediate 119, 347 mg, 0.70 mmol), iron (235 mg, 4.22 mmol) and NH4Cl (26.3 mg, 0.49 mmol) in ethanol (9 mL) and water (3 mL) was heated at reflux for 1 h. The mixture was then purified by ion exchange chromatography, using an SCX column and eluting with 7M methanolic ammonia. Appropriate fractions were combined and concentrated in vacuo onto silica. Further purification by FCC, eluting with 0-5% 7M methanolic ammonia in CH2Cl2 gave the title compound (323 mg, 99%) as a tan solid; 1H NMR: 2.12 (6H, s), 3.06 (1H, p), 3.48 (2H, t), 3.68 (3H, s), 3.92-4.02 (4H, m), 6.28 (1H, s), 6.91 (1H, s), 7.04 (1H, dd), 7.12-7.19 (1H, m), 7.44 (1H, d), 8.14 (1H, s), 8.28 (1H, s), 8.30 (1H, d), 8.46 (1H, s), 11.77 (1H, s); m/z: ES+ MH+ 464.21.

Aufarbeitung

  1. temperaturewas heated
  2. temperatureat reflux for 1 h
  3. customThe mixture was then purified by ion exchange chromatography
  4. washeluting with 7M methanolic ammonia
  5. concentrationconcentrated in vacuo onto silica
  6. customFurther purification by FCC
  7. washeluting with 0-5% 7M methanolic ammonia in CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-be4a0da03c3046bba0160b527e3c6300
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946235B2

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