Ethanol → 4-[(3S)-3-dimethylaminopyrrolidin-1-yl]-6-methoxy-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamine

HRID 1842801Notes

Reaction equation

HRID 1842801 reaction equation
[CH3:1][N:2]([CH3:36])[C@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[C:13]([N+:14]([O-])=O)=[CH:12][C:11]([NH:17][C:18]3[N:23]=[C:22]([C:24]4[C:32]5[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=5)[N:26]([CH3:33])[CH:25]=4)[CH:21]=[CH:20][N:19]=3)=[C:10]([O:34][CH3:35])[CH:9]=2)[CH2:4]1.[NH4+].[Cl-].C(O)C>[Fe].O>[CH3:36][N:2]([CH3:1])[C@H:3]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[C:10]([O:34][CH3:35])[C:11]([NH:17][C:18]3[N:23]=[C:22]([C:24]4[C:32]5[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=5)[N:26]([CH3:33])[CH:25]=4)[CH:21]=[CH:20][N:19]=3)=[CH:12][C:13]=2[NH2:14])[CH2:4]1

Participants

6

Reactant 3

HCID 702EthanolHCID 25517Ammonium Chloride2×HCID 71270238N-[4-[(3S)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine2×

Product 1

HCID 866773054-[(3S)-3-dimethylaminopyrrolidin-1-yl]-6-methoxy-N-[4-(1-methylindol-3-yl)pyrimidin-2-yl]benzene-1,3-diamineYield 87%

Reagents, catalysts & solvents 2

HCID 23925IronCatalyst2×HCID 962WaterSolvent

Procedure

A mixture of N-[4-[(3S)-3-dimethylaminopyrrolidin-1-yl]-2-methoxy-5-nitrophenyl]-4-(1-methylindol-3-yl)pyrimidin-2-amine (Intermediate 149, 230 mg, 0.47 mmol), iron (158 mg, 2.83 mmol), NH4Cl (17.7 mg, 0.33 mmol), ethanol (9 mL) and water (3 mL) was heated at reflux for 50 minutes. The reaction was judged to be incomplete so further iron (158 mg, 2.83 mmol) and NH4Cl (17.7 mg, 0.33 mmol) was added and the mixture was heated at reflux for a further 0.5 h. After cooling, the mixture was filtered and concentrated in vacuo. Purification by FCC, eluting with 1.5-7% 7M methanolic ammonia in CH2Cl2 gave the title compound (187 mg, 87%) as a grey foam; 1H NMR: 1.78 (1H, m), 2.06 (1H, m), 2.20 (6H, s), 2.86 (1H, d), 2.90-3.01 (2H, m), 3.12 (1H, m), 3.15-3.23 (1H, m), 3.76 (3H, s), 3.88 (3H, s), 4.27 (2H, s), 6.72 (1H, s), 7.14 (1H, d), 7.15-7.21 (1H, m), 7.22-7.34 (1H, m), 7.50 (1H, s), 7.52 (1H, d), 7.74 (1H, s), 8.26 (1H, s), 8.28 (1H, s), 8.43 (1H, d); m/z: ES+ MH+ 458.75.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 50 minutes
  3. additionwas added
  4. temperaturethe mixture was heated
  5. temperatureat reflux for a further 0.5 h
  6. temperatureAfter cooling
  7. filtrationthe mixture was filtered
  8. concentrationconcentrated in vacuo
  9. customPurification by FCC
  10. washeluting with 1.5-7% 7M methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-bb30d5cd483f456f80c07cf8ca1ed0ed
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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