4-Chloroaniline → N-(4-chloro-phenyl)-4-(2-chloro-pyrimidin-4-yl)-benzamide

HRID 1693558Notes

Reaction equation

HRID 1693558 reaction equation
O[C:2]1[N:7]=[C:6]([C:8]2[CH:16]=[CH:15][C:11]([C:12]([OH:14])=O)=[CH:10][CH:9]=2)[CH:5]=[CH:4][N:3]=1.O=P(Cl)(Cl)[Cl:19].[Cl:22][C:23]1[CH:29]=[CH:28][C:26]([NH2:27])=[CH:25][CH:24]=1.CCN(CC)CC>O>[Cl:22][C:23]1[CH:29]=[CH:28][C:26]([NH:27][C:12](=[O:14])[C:11]2[CH:10]=[CH:9][C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([Cl:19])[N:7]=3)=[CH:16][CH:15]=2)=[CH:25][CH:24]=1

Participants

6

Reactant 4

HCID 78124-ChloroanilineHCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 178524219HCID 178524219, compound

Product 1

HCID 57897981N-(4-chloro-phenyl)-4-(2-chloro-pyrimidin-4-yl)-benzamideYield 44%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

The crude 4-(2-hydroxy-pyrimidin-4-yl)-benzoic acid is treated with POCl3 (4 mL) at 100° C. for 14 h and cooled down to room temperature. POCl3 is removed under vacuum and the residue is flushed once with toluene (3 mL). The residue is dissolved in anhydrous dichloromethane (4 mL) and put into ice bath. 4-Chloroaniline (790 mg, 6.28 mmol) is added followed by the addition of Et3N (1.2 g, 12 mmol). After stirring at 0° C. for 1 h, the mixture is poured into water (100 mL) and extracted with EtOAc (3×50 mL). The combined extracts is washed with brine, dried (MgSO4) and concentrated. The residue is purified by flash column chromatography (silica gel, 0-80% EtOAc/hexane) to provide the desired N-(4-chloro-phenyl)-4-(2-chloro-pyrimidin-4-yl)-benzamide as yellow solid (650 mg, 44%). HPLC-MS calculated C17H11Cl2N3O (M+1+): 344.0. Found: 344.0.

Workup

  1. customPOCl3 is removed under vacuum
  2. customthe residue is flushed once with toluene (3 mL)
  3. dissolutionThe residue is dissolved in anhydrous dichloromethane (4 mL)
  4. customput into ice bath
  5. extractionextracted with EtOAc (3×50 mL)
  6. washThe combined extracts is washed with brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue is purified by flash column chromatography (silica gel, 0-80% EtOAc/hexane)

Sources & evidence

ORD record
ord-8872ba9a298d43ff82e62e0c11717d90
Source dataset
uspto-grants-2012_04
Patent number
US08158634B2

Reaction notes

Loading…