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

HRID 1842766Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1842766
[Cl:1][C:2]1[C:3]([C:27]2[C:35]3[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=3)[N:29]([CH3:36])[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)[N:29]([CH3:36])[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[CH2:19][CH:20]([N:22]([CH3:24])[CH3:23])[CH2:21]3)=[C:13]([NH2:15])[CH:14]=2)=[N:6][CH:7]=1

Komponenten

6

Edukt 2

HCID 25517Ammonium ChlorideHCID 712408245-chloro-N-[4-(3-dimethylaminoazetidin-1-yl)-2-methoxy-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine2×

Produkt 1

HCID 86677279N-[5-chloro-4-(1-methylindol-3-yl)pyrimidin-2-yl]-4-(3-dimethylaminoazetidin-1-yl)-6-methoxybenzene-1,3-diamineAusbeute 98,3 %

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-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 113, 285 mg, 0.56 mmol), iron (188 mg, 3.37 mmol) and NH4Cl (22.51 mg, 0.42 mmol) in ethanol (9 mL) and water (3 mL) was heated at reflux for 2 h. The mixture was then cooled and filtered through diatomaceous earth (Celite™). The filtrate was concentrated in vacuo and the resulting residue was dissolved in CH2Cl2. This solution was washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 1-20% 7N methanolic ammonia in CH2Cl2 gave the title compound (263 mg, 98%) as a brown dry film; 1H NMR: (CDCl3) 2.21 (6H, s), 3.08-3.18 (1H, m), 3.30 (2H, br s), 3.58 (2H, t), 3.86 (3H, s), 3.88 (3H, s), 3.93 (2H, t), 6.38 (1H, s), 7.2-7.42 (3H, m, partially obscured by chloroform signal), 7.50 (1H, s), 7.99 (1H, s), 8.20 (1H, s), 8.31 (1H, s), 8.63 (1H, d); m/z: ES+ MH+ 478.

Aufarbeitung

  1. temperaturewas heated
  2. temperatureat reflux for 2 h
  3. temperatureThe mixture was then cooled
  4. filtrationfiltered through diatomaceous earth (Celite™)
  5. concentrationThe filtrate was concentrated in vacuo
  6. dissolutionthe resulting residue was dissolved in CH2Cl2
  7. washThis solution was washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customPurification by FCC
  11. washeluting with 1-20% 7N methanolic ammonia in CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-f91bbf22da9d49de87bf2328480abea4
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946235B2

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