Benzylamine → HCID 178490948, compound

HRID 232790Notes

Reaction equation

HRID 232790 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:25])[C:7]=1[NH:8][C:9](=O)[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH:11]=1.P(Cl)(Cl)(Cl)=O.[CH2:31]([NH2:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>CN(C)C1C=CC=CC=1>[CH2:31]([NH:38][C:9](=[N:8][C:7]1[C:2]([Cl:1])=[CH:3][N:4]=[CH:5][C:6]=1[Cl:25])[C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH:19]2[CH2:23][CH2:22][CH2:21][CH2:20]2)[CH:11]=1)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

5

Reactant 3

HCID 7504BenzylamineHCID 24813Phosphorus oxychlorideHCID 154575Piclamilast

Product 1

HCID 178490948HCID 178490948, compoundYield 50.6%

Reagents, catalysts & solvents 1

HCID 949N,N-DimethylanilineSolvent

Procedure

A solution of N-(3,5-dichloropyrid-4-yl)-3-cyclopentyloxy-4-methoxybenzamide (1 gram, 2.62 mmol) in phosphoryl chloride (15 milliliters, 161 mmol) and N, N-dimethylaniline (0.75 milliliters) was refluxed under nitrogen for 20 hours. The mixture was cooled to room temperature, volatiles removed in-vacuo, and the brown residue azeotroped with toluene (3×20 milliliters). The crude imino chloride was dissolved in toluene (15 milliliters), an excess of benzylamine (2.57 milliliters, 23.58 mmol) was added in one portion and the mixture refluxed, under nitrogen, for 4 hours. The mixture was cooled to room temperature, volatiles removed in-vacuo, and the residue dissolved in chloroform (100 milliliters) and washed with water (2×50 milliliters). The combined organics were dried (Na2SO4) and volatiles removed in-vacuo to yield a white solid. The mixture was purified by flash chromatography (SiO2 ; ethyl acetate: hexane (1:9), followed by ethyl acetate: hexane (1:4)) to yield the title compound (624 milligrams, 50 %) as a white crystalline solid, m.p. 129°-133° C.

Workup

  1. customvolatiles removed in-vacuo
  2. customthe brown residue azeotroped with toluene (3×20 milliliters)
  3. dissolutionThe crude imino chloride was dissolved in toluene (15 milliliters)
  4. temperaturethe mixture refluxed, under nitrogen, for 4 hours
  5. temperatureThe mixture was cooled to room temperature
  6. customvolatiles removed in-vacuo
  7. dissolutionthe residue dissolved in chloroform (100 milliliters)
  8. washwashed with water (2×50 milliliters)
  9. dry with materialThe combined organics were dried (Na2SO4)
  10. customvolatiles removed in-vacuo
  11. customto yield a white solid
  12. customThe mixture was purified by flash chromatography (SiO2 ; ethyl acetate: hexane (1:9), followed by ethyl acetate: hexane (1:4))

Sources & evidence

ORD record
ord-35016150c4ea483b842f67df0712ad31
Source dataset
uspto-grants-1997_01
Patent number
US05591776

Reaction notes

Loading…