Ammonium Chloride → 4-methoxy-6-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-N'-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamine

HRID 1842803Notes

Reaction equation

HRID 1842803 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]2[CH2:10][CH2:11][N:12]([CH3:15])[CH2:13][CH:14]=2)[C:6]([N+:16]([O-])=O)=[CH:5][C:4]=1[NH:19][C:20]1[N:25]=[C:24]([C:26]2[CH:27]=[N:28][N:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=23)[CH:23]=[CH:22][N:21]=1.[NH4+].[Cl-]>[Fe].O>[CH3:1][O:2][C:3]1[CH:8]=[C:7]([C:9]2[CH2:10][CH2:11][N:12]([CH3:15])[CH2:13][CH:14]=2)[C:6]([NH2:16])=[CH:5][C:4]=1[NH:19][C:20]1[N:25]=[C:24]([C:26]2[CH:27]=[N:28][N:29]3[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=23)[CH:23]=[CH:22][N:21]=1

Participants

5

Reactant 2

HCID 25517Ammonium Chloride2×HCID 71240769HCID 71240769, compound2×

Product 1

HCID 866773074-methoxy-6-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-N'-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,3-diamineYield 76.4%

Reagents, catalysts & solvents 2

HCID 23925IronCatalyst2×HCID 962WaterSolvent

Procedure

A mixture of N-[2-methoxy-4-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-5-nitrophenyl]-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 151, 285 mg, 0.56 mmol), iron (188 mg, 3.36 mmol), NH4Cl (21 mg, 0.39 mmol) ethanol (10.5 mL) and water (3.5 mL) was heated at reflux for 1.5 h. The reaction was judged to be incomplete so further NH4Cl (21 mg, 0.39 mmol) and iron (188 mg, 3.36 mmol) were added and the mixture was heated at reflux for a further 1.5 h. After cooling, the mixture was filtered and concentrated in vacuo. Purification by FCC, eluting with 2-10% 7N methanolic ammonia in CH2Cl2 gave the title compound (183 mg, 69%) as an orange gum which was used without further purification; 1H NMR: 2.30 (3H, s), 2.36-2.45 (2H, m), 2.60 (2H, t), 2.98-3.06 (2H, m), 3.74 (3H, s), 4.34 (2H, s), 5.73 (1H, s), 6.64 (1H, s), 7.09 (1H, m), 7.26 (1H, d), 7.38-7.49 (2H, m), 8.00 (1H, s), 8.35 (1H, d), 8.58 (1H, d), 8.80 (2H, m); m/z: ES+ MH+ 427.

Workup

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

Sources & evidence

ORD record
ord-a2fb77aa3d43496082f4b88e8cb14c63
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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