Water → 4-bromo-6-methoxy-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamine

HRID 1842797Notes

Reaction equation

HRID 1842797 reaction equation
[Br:1][C:2]1[C:7]([N+:8]([O-])=O)=[CH:6][C:5]([NH:11][C:12]2[N:17]=[C:16]([C:18]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]([CH3:27])[CH:19]=3)[CH:15]=[CH:14][N:13]=2)=[C:4]([O:28][CH3:29])[CH:3]=1.[NH4+].[Cl-].O>C(O)C.[Fe]>[Br:1][C:2]1[CH:3]=[C:4]([O:28][CH3:29])[C:5]([NH:11][C:12]2[N:17]=[C:16]([C:18]3[C:26]4[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=4)[N:20]([CH3:27])[CH:19]=3)[CH:15]=[CH:14][N:13]=2)=[CH:6][C:7]=1[NH2:8]

Participants

6

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 71239107N-(4-bromo-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine2×

Product 1

HCID 866773474-bromo-6-methoxy-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamineYield 93.6%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Procedure

N-(4-Bromo-2-methoxy-5-nitrophenyl)-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 145, 1.074 g, 2.36 mmol), iron (0.792 g, 14.19 mmol) and NH4Cl (95 mg, 1.77 mmol) were heated at reflux in ethanol (39 mL) and water (13 mL) for 1.5 h. The mixture was then cooled and concentrated in vacuo. The resulting residue was triturated in 10% CH3OH in CH2Cl2 (30 mL) for 15 minutes and the mixture was then filtered. The residues were triturated again with 10% CH3OH in CH2Cl2 (30 mL) and the mixture then filtered. The combined filtrates were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with CH2Cl2 gave the title compound (0.937 g, 93%) as a cream foam; 1H NMR: 3.79 (3H, s), 3.89 (3H, s), 4.86 (2H, s), 7.06 (1H, s), 7.18-7.30 (3H, m), 7.54 (1H, d), 7.83 (1H, s), 7.87 (1H, s), 8.33 (1H, d), 8.35 (1H, s), 8.43 (1H, d); m/z: ES+ MH+ 424/426.

Workup

  1. temperatureThe mixture was then cooled
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was triturated in 10% CH3OH in CH2Cl2 (30 mL) for 15 minutes
  4. filtrationthe mixture was then filtered
  5. customThe residues were triturated again with 10% CH3OH in CH2Cl2 (30 mL)
  6. filtrationthe mixture then filtered
  7. washThe combined filtrates were washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated in vacuo
  10. customPurification by FCC
  11. washeluting with CH2Cl2

Sources & evidence

ORD record
ord-9369c0cebf1c4912983a2d3e35184535
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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