Ammonium Chloride → 4-(3-dimethylaminoazetidin-1-yl)-6-methoxy-N-[5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamine

HRID 1842768Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1842768
[CH3:1][N:2]([CH3:36])[CH:3]1[CH2:6][N:5]([C:7]2[C:12]([N+:13]([O-])=O)=[CH:11][C:10]([NH:16][C:17]3[N:22]=[C:21]([C:23]4[C:31]5[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=5)[N:25]([CH3:32])[CH:24]=4)[C:20]([CH3:33])=[CH:19][N:18]=3)=[C:9]([O:34][CH3:35])[CH:8]=2)[CH2:4]1.[NH4+].[Cl-]>C(O)C.O.[Fe]>[CH3:36][N:2]([CH3:1])[CH:3]1[CH2:4][N:5]([C:7]2[CH:8]=[C:9]([O:34][CH3:35])[C:10]([NH:16][C:17]3[N:22]=[C:21]([C:23]4[C:31]5[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=5)[N:25]([CH3:32])[CH:24]=4)[C:20]([CH3:33])=[CH:19][N:18]=3)=[CH:11][C:12]=2[NH2:13])[CH2:6]1

Komponenten

6

Edukt 2

HCID 25517Ammonium ChlorideHCID 71240800N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-amine2×

Produkt 1

HCID 866772814-(3-dimethylaminoazetidin-1-yl)-6-methoxy-N-[5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamineAusbeute 69 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23925IronKatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

A mixture of N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 115, 210 mg, 0.43 mmol), iron (144 mg, 2.58 mmol) and NH4Cl (16.13 mg, 0.30 mmol) in ethanol (6 mL) and water (2 mL) were heated at reflux for 2 h. The crude mixture was 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% 7N methanolic ammonia in CH2Cl2 gave a brown foam after concentration of appropriate fractions in vacuo. Further purification by ion exchange chromatography, using an SCX column and eluting with 7M methanolic ammonia provided material that was concentrated in vacuo onto silica. Further purification by FCC, eluting with 0-4% CH3OH in CH2Cl2 gave the title compound (135 mg, 69%) as a brown foam; 1H NMR: 2.11 (6H, s), 2.35 (3H, s), 3.04 (1H, p), 3.44 (2H, t), 3.89 (3H, s), 3.92 (2H, s), 3.9-3.97 (2H, m), 6.28 (1H, s), 7.12 (1H, dd), 7.2-7.26 (1H, m), 7.28 (1H, s), 7.48 (1H, d), 7.55 (1H, s), 8.00 (1H, s), 8.15 (1H, s), 8.43 (1H, d); m/z: ES+ MH+ 458.31.

Aufarbeitung

  1. temperaturewere heated
  2. temperatureat reflux for 2 h
  3. customThe crude mixture was 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% 7N methanolic ammonia in CH2Cl2
  8. customgave a brown foam after concentration of appropriate fractions in vacuo
  9. customFurther purification by ion exchange chromatography
  10. washeluting with 7M methanolic ammonia provided material that
  11. concentrationwas concentrated in vacuo onto silica
  12. customFurther purification by FCC
  13. washeluting with 0-4% CH3OH in CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-a8c320b59c4140d7a9d5e047ff0ba57f
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946235B2

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