Ethyl Acetate → N-cyclopropyl-4-methyl-3-{[4-(pyridin-2-ylmethoxy)benzoyl]amino}benzamide

HRID 403028Notes

Reaction equation

HRID 403028 reaction equation
[CH:1]1([NH:4][C:5](=[O:23])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([NH:13][C:14](=[O:22])[C:15]3[CH:20]=[CH:19][C:18]([OH:21])=[CH:17][CH:16]=3)[CH:7]=2)[CH2:3][CH2:2]1.C(=O)([O-])[O-].[K+].[K+].Cl.Cl[CH2:32][C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=1.C(OCC)(=O)C>CN(C=O)C>[CH:1]1([NH:4][C:5](=[O:23])[C:6]2[CH:11]=[CH:10][C:9]([CH3:12])=[C:8]([NH:13][C:14](=[O:22])[C:15]3[CH:16]=[CH:17][C:18]([O:21][CH2:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=4)=[CH:19][CH:20]=3)[CH:7]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium Carbonate2×HCID 23392Picolyl chloride hydrochlorideHCID 66631169N-cyclopropyl-3-[(4-hydroxybenzoyl)amino]-4-methylbenzamide

Product 1

HCID 11475107N-cyclopropyl-4-methyl-3-{[4-(pyridin-2-ylmethoxy)benzoyl]amino}benzamideYield 65.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of N-cyclopropyl-3-[(4-hydroxybenzoyl)amino]-4-methylbenzamide (500 mg, 1.61 mmol) in DMF (2.5 mL) was added potassium carbonate (446 mg, 3.22 mmol). The resulting mixture was stirred at room temperature for 15 minutes. 2-Chloromethyl-pyridine hydrochloride (291 mg, 1.78 mmol) was added and the resulting mixture stirred and heated to 50° C. for 18 h. The mixture was cooled to room temperature and saturated aqueous potassium carbonate solution (15 mL) and ethyl acetate (5 mL) were added. The resulting mixture was stirred for 20 minutes. The solid was collected by filtration, washed with saturated aqueous potassium carbonate solution, ethyl acetate and isohexane and dried giving the title compound as a solid (425 mg, 60%); NMR Spectrum: (DMSOd6) 0.56 (m, 2H), 0.68 (m, 2H), 2.29 (s, 3H), 2.86 (m, 1H), 5.33 (s, 2H), 7.16 (m, 2H), 7.34 (m, 2H), 7.55 (m, 1H), 7.62 (m, 1H), 7.81 (s, 1H), 7.86 (m, 1H), 7.98 (m, 2H), 8.36 (s, 1H), 8.60 (m, 1H), 10.00 (s, 1H); Mass Spectrum: M+H+ 401.

Workup

  1. stirringthe resulting mixture stirred
  2. temperatureheated to 50° C. for 18 h
  3. temperatureThe mixture was cooled to room temperature
  4. stirringThe resulting mixture was stirred for 20 minutes
  5. filtrationThe solid was collected by filtration
  6. washwashed with saturated aqueous potassium carbonate solution, ethyl acetate and isohexane
  7. customdried

Sources & evidence

ORD record
ord-a291340ba0eb4b82b6e76c78cb2d5dab
Source dataset
uspto-grants-2014_06
Patent number
US08742124B2

Reaction notes

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