Methanol → 4-methoxy-N'-[5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-yl]-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine

HRID 1842734Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1842734
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)[C:6]([N+:16]([O-])=O)=[CH:5][C:4]=1[NH:19][C:20]1[N:25]=[C:24]([C:26]2[C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[N:28]([CH3:35])[CH:27]=2)[C:23]([CH3:36])=[CH:22][N:21]=1.[NH4+].[Cl-].C(Cl)Cl.CO>C(O)C.O.[Fe]>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[CH2:11][CH2:10]2)[C:6]([NH2:16])=[CH:5][C:4]=1[NH:19][C:20]1[N:25]=[C:24]([C:26]2[C:34]3[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=3)[N:28]([CH3:35])[CH:27]=2)[C:23]([CH3:36])=[CH:22][N:21]=1

Komponenten

8

Edukt 4

HCID 887MethanolHCID 6344DichloromethaneHCID 25517Ammonium ChlorideHCID 71240823N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]-5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-amine2×

Produkt 1

HCID 866772524-methoxy-N'-[5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-yl]-6-(4-methylpiperazin-1-yl)benzene-1,3-diamineAusbeute 43 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23925IronKatalysatorHCID 702EthanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

A mixture of N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]-5-methyl-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 78, 408 mg, 0.84 mmol), iron (280 mg, 5.02 mmol) and NH4Cl (31.3 mg, 0.59 mmol) in ethanol (24 mL) and water (8.00 mL) was heated at reflux for 3 h. The mixture was cooled and concentrated in vacuo to give a thick slurry. CH2Cl2 (100 mL) and CH3OH (10 mL) were added and the mixture was stirred for 0.25 h and then filtered. The filter cake was washed with further CH2Cl2 and CH3OH and the combined organics were dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 1-7% methanolic ammonia in CH2Cl2 gave the title compound (163 mg, 43%) as a yellow gum which crystallised on standing; 1H NMR: (CDCl3) 2.36 (6H, s), 2.53 (3H, dd), 2.94 (4H, t), 3.69-3.79 (2H, m), 3.83 (3H, s), 3.86 (3H, s), 6.69 (1H, s), 7.24-7.27 (1H, m), 7.29 (1H, dd), 7.33 (1H, dd), 7.36-7.40 (1H, m), 7.49 (1H, s), 7.58 (1H, s), 8.23 (1H, d), 8.26 (1H, s), 8.56 (1H, d); m/z: ES+ MH+ 458.37.

Aufarbeitung

  1. temperaturewas heated
  2. temperatureat reflux for 3 h
  3. temperatureThe mixture was cooled
  4. concentrationconcentrated in vacuo
  5. customto give a thick slurry
  6. filtrationfiltered
  7. washThe filter cake was washed with further CH2Cl2 and CH3OH
  8. dry with materialthe combined organics were dried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customPurification by FCC
  11. washeluting with 1-7% methanolic ammonia in CH2Cl2

Quellen und Nachweise

ORD-Eintrag
ord-0492777d29af4b73bfe7f2e856bfece3
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08946235B2

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