Ethanol → N1-(2-dimethylaminoethyl)-5-methoxy-N1-methyl-N4-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,2,4-triamine

HRID 1842810Notes

Reaction equation

HRID 1842810 reaction equation
[CH3:1][N:2]([CH3:34])[CH2:3][CH2:4][N:5]([CH3:33])[C:6]1[C:11]([N+:12]([O-])=O)=[CH:10][C:9]([NH:15][C:16]2[N:21]=[C:20]([C:22]3[CH:23]=[N:24][N:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=34)[CH:19]=[CH:18][N:17]=2)=[C:8]([O:31][CH3:32])[CH:7]=1.[NH4+].[Cl-].C(O)C>[Fe].O>[CH3:34][N:2]([CH3:1])[CH2:3][CH2:4][N:5]([CH3:33])[C:6]1[C:11]([NH2:12])=[CH:10][C:9]([NH:15][C:16]2[N:21]=[C:20]([C:22]3[CH:23]=[N:24][N:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=34)[CH:19]=[CH:18][N:17]=2)=[C:8]([O:31][CH3:32])[CH:7]=1

Participants

6

Reactant 3

HCID 702EthanolHCID 25517Ammonium ChlorideHCID 71270077N'-(2-dimethylaminoethyl)-2-methoxy-N'-methyl-5-nitro-N-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,4-diamine2×

Product 1

HCID 86677313N1-(2-dimethylaminoethyl)-5-methoxy-N1-methyl-N4-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,2,4-triamineYield 78.1%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 962WaterSolvent

Procedure

A mixture of N′-(2-dimethylaminoethyl)-2-methoxy-N′-methyl-5-nitro-N-(4-pyrazolo[1,5-a]pyridin-3-ylpyrimidin-2-yl)benzene-1,4-diamine (Intermediate 159, 440 mg, 0.95 mmol), iron (319 mg, 5.71 mmol), NH4Cl (38.2 mg, 0.71 mmol), ethanol (15 mL) and water (5 mL) was heated at reflux for 1.5 h. After cooling, the mixture was concentrated in vacuo. The resulting residue was triturated in 10% CH3OH in CH2Cl2 (20 mL) for 15 minutes and the mixture was then filtered. The residues were triturated again with 10% CH3OH in CH2Cl2 (20 mL) and then filtered. The combined filtrates were washed with brine, dried (MgSO4) and concentrated in vacuo. Purification by FCC, eluting with 0-10% methanolic ammonia in CH2Cl2 gave the title compound (321 mg, 78%) as a brown gum after trituration with diethyl ether; 1H NMR: 2.18 (6H, s), 2.37 (2H, t), 2.65 (3H, s), 2.91 (2H, t), 3.72 (3H, s), 4.57 (2H, br s), 6.77 (1H, s), 7.07 (1H, td), 7.22 (1H, d), 7.29 (1H, s), 7.37-7.42 (1H, m), 7.97 (1H, s), 8.31 (1H, d), 8.52 (1H, d), 8.76 (1H, s), 8.77-8.80 (1H, m); m/z: ES+ MH+ 433.36.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 1.5 h
  3. temperatureAfter cooling
  4. concentrationthe mixture was concentrated in vacuo
  5. customThe resulting residue was triturated in 10% CH3OH in CH2Cl2 (20 mL) for 15 minutes
  6. filtrationthe mixture was then filtered
  7. customThe residues were triturated again with 10% CH3OH in CH2Cl2 (20 mL)
  8. filtrationfiltered
  9. washThe combined filtrates were washed with brine
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. customPurification by FCC
  13. washeluting with 0-10% methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-75e0467be58e4f469c07b2d452303fa3
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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