Ethanol → 4-Methoxy-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]-6-(4-methylpiperazin-1-yl)benzene-1,3-diamine

HRID 1842764Notes

Reaction equation

HRID 1842764 reaction equation
CO[C:3]1[CH:8]=[C:7](N2CCN(C)CC2)[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)[CH:23]=[CH:22][N:21]=1.[NH4+:36].[Cl-].[CH2:38]([OH:40])C>O.[Fe]>[CH3:38][O:40][C:7]1[CH:8]=[C:3]([N:36]2[CH2:30][CH2:29][N:28]([CH3:35])[CH2:27][CH2:26]2)[C:4]([NH:19][C:20]2[N:25]=[C:24]([C:26]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[N:28]([CH3:35])[CH:27]=3)[CH:23]=[CH:22][N:21]=2)=[CH:5][C:6]=1[NH2:16]

Participants

6

Reactant 3

HCID 702EthanolHCID 25517Ammonium ChlorideHCID 71240791N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine2×

Product 1

HCID 866773424-Methoxy-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]-6-(4-methylpiperazin-1-yl)benzene-1,3-diamineYield 93%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 962WaterSolvent

Procedure

A mixture of N-[2-methoxy-4-(4-methylpiperazin-1-yl)-5-nitrophenyl]-4-(1-methy-lindol-3-yl)pyrimidin-2-amine (Intermediate 111, 329 mg, 0.69 mmol), iron (233 mg, 4.17 mmol) and NH4Cl (26.0 mg, 0.49 mmol) in ethanol (12 mL) and water (4 mL) were heated at reflux for 3 h. The mixture was allowed to cool to r.t. and then filtered. The filtrate was concentrated in vacuo. Purification by ion exchange chromatography, using an SCX column and eluting with 0.7M methanolic ammonia gave a brown gum after concentration of appropriate fractions in vacuo. Further purification by FCC, eluting with 0-5% 7N methanolic ammonia in CH2Cl2 gave the title compound (287 mg, 93%) as a light brown gum; 1H NMR: (CDCl3) 2.37 (3H, br s), 2.59 (4H, s), 2.92-2.99 (4H, m), 3.79-3.86 (5H, m), 3.87 (3H, s), 6.71 (1H, s), 7.01 (1H, d), 7.27-7.34 (2H, m), 7.35-7.40 (1H, m), 7.57 (1H, s), 7.78 (1H, s), 8.17 (1H, s), 8.32 (1H, d), 8.47-8.53 (1H, m); m/z: ES+ MH+ 444.54.

Workup

  1. temperaturewere heated
  2. temperatureat reflux for 3 h
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated in vacuo
  5. customPurification by ion exchange chromatography
  6. washeluting with 0.7M methanolic ammonia
  7. customgave a brown gum after concentration of appropriate fractions in vacuo
  8. customFurther purification by FCC
  9. washeluting with 0-5% 7N methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-7f98c34ba9704e93a2f0a81491760ca4
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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