Water → HCID 86677291, compound

HRID 1842779Notes

Reaction equation

HRID 1842779 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[CH2:30][CH2:29][CH2:28][CH2:27][C:26]=34)[CH:19]=[CH:18][N:17]=2)=[C:8]([O:31][CH3:32])[CH:7]=1.[NH4+].[Cl-].O>C(O)C.[Fe]>[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[CH2:30][CH2:29][CH2:28][CH2:27][C:26]=34)[CH:19]=[CH:18][N:17]=2)=[C:8]([O:31][CH3:32])[CH:7]=1

Participants

6

Reactant 3

HCID 962WaterHCID 25517Ammonium ChlorideHCID 71269982HCID 71269982, compound2×

Product 1

HCID 86677291HCID 86677291, compoundYield 72.2%

Reagents, catalysts & solvents 2

HCID 23925IronCatalystHCID 702EthanolSolvent

Procedure

A mixture of N′-(2-dimethylaminoethyl)-2-methoxy-N′-methyl-5-nitro-N-[4-(4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)pyrimidin-2-yl]benzene-1,4-diamine (Intermediate 126, 3.7 g, 7.93 mmol), iron (2.66 g, 47.58 mmol) and NH4Cl (0.318 g, 5.95 mmol) was heated in ethanol (120 mL) and water (40 mL) at reflux for 2.5 h. The mixture was then cooled, filtered and concentrated. The solids were triturated in 5% CH3OH/CH2Cl2 (100 mL) for 15 minutes and then filtered. The filtrate was combined with the concentrated, filtered reaction mixture, washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification by FCC, eluting with 0-2.5% 7N methanolic ammonia in CH2Cl2 gave the title compound (2.50 g, 72%) as a brown gum; 1H NMR (CDCl3): 1.90-1.99 (2H, m), 2.04-2.13 (2H, m), 2.25 (6H, s), 2.37-2.42 (2H, m), 2.67 (3H, s), 2.92-2.98 (2H, m), 3.25 (2H, t), 3.83 (3H, s), 4.00 (2H, s), 4.21 (2H, t), 6.70 (1H, s), 6.79 (1H, d), 7.48 (1H, s), 7.97 (2H, d), 8.30 (1H, d); m/z: ES+ MH+ 437.39.

Workup

  1. temperatureThe mixture was then cooled
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customThe solids were triturated in 5% CH3OH/CH2Cl2 (100 mL) for 15 minutes
  5. filtrationfiltered
  6. filtrationfiltered
  7. customreaction mixture
  8. washwashed with brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customPurification by FCC
  12. washeluting with 0-2.5% 7N methanolic ammonia in CH2Cl2

Sources & evidence

ORD record
ord-7b9f894f98404232a640a9e270427cbc
Source dataset
uspto-grants-2015_02
Patent number
US08946235B2

Reaction notes

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