Ammonium Chloride → HCID 86677324, compound

HRID 1842669Notes

Reaction equation

HRID 1842669 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)[C:23]([CH3:35])=[CH:22][N:21]=1.[NH4+].[Cl-]>C(O)C.O.[Fe]>[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)[C:23]([CH3:35])=[CH:22][N:21]=1

Participants

6

Reactant 2

HCID 25517Ammonium Chloride2×HCID 71240803HCID 71240803, compound2×

Product 1

HCID 86677324HCID 86677324, compoundYield 57.6%

Reagents, catalysts & solvents 3

HCID 23925IronCatalyst2×HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A mixture of N-[2-methoxy-4-(1-methyl-3,6-dihydro-2H-pyridin-4-yl)-5-nitrophenyl]-5-methyl-4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-amine (Intermediate 2, 279 mg, 0.59 mmol), iron (198 mg, 3.55 mmol) and NH4Cl (22.16 mg, 0.41 mmol) in ethanol (10.5 mL) and water (3.50 mL) was heated at reflux for 0.75 h. Further NH4Cl (22.16 mg, 0.41 mmol) and iron (198 mg, 3.55 mmol) were then added and the mixture was heated at reflux for a further 1.5 h. The mixture was then cooled, filtered, and the filtrate was concentrated in vacuo. Purification by FCC, eluting with 2-10% 7N methanolic ammonia in CH2Cl2 gave the title compound (150 mg, 57%) as a beige crystalline solid after trituration with THF and washing the resulting solid with diethyl ether; 1H NMR: 2.30 (3H, s), 2.40 (5H, m), 2.59 (2H, t), 3.01 (2H, d), 3.73 (3H, s), 4.27 (2H, s), 5.71 (1H, s), 6.63 (1H, s), 7.10 (1H, m), 7.35-7.49 (2H, m), 7.83 (1H, s), 8.27 (1H, s), 8.50-8.63 (2H, m), 8.81 (1H, d); m/z: ES+ MH+ 442.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 0.75 h
  3. temperaturethe mixture was heated
  4. temperatureat reflux for a further 1.5 h
  5. temperatureThe mixture was then cooled
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated in vacuo
  8. customPurification by FCC
  9. washeluting with 2-10% 7N methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-d0085a99c57a43668fdb136c80b35075
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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