Phenylacetyl chloride → 3-Benzyl-7-(4-bromo-2-chlorophenylamino)-8-chloro-[1,2,4]triazolo[4,3-a]pyridine-6-carboxylic acid methyl ester

HRID 917029Notes

Reaction equation

HRID 917029 reaction equation
[C:1]1([CH2:7][C:8](Cl)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:11]([O:13][C:14](=[O:33])[C:15]1[C:20]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][C:23]=2[Cl:29])=[C:19]([Cl:30])[C:18]([NH:31][NH2:32])=[N:17][CH:16]=1)C.C(N(CC)CC)C.O=P(Cl)(Cl)Cl>C(Cl)Cl.C(Cl)CCl>[CH3:11][O:13][C:14]([C:15]1[C:20]([NH:21][C:22]2[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][C:23]=2[Cl:29])=[C:19]([Cl:30])[C:18]2[N:17]([C:8]([CH2:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[N:32][N:31]=2)[CH:16]=1)=[O:33]

Participants

7

Reactant 4

HCID 7679Phenylacetyl chloride2×HCID 8471TriethylamineHCID 24813Phosphorus oxychlorideHCID 688607444-(4-Bromo-2-chlorophenylamino)-5-chloro-6-hydrazinonicotinic acid ethyl ester

Product 1

HCID 688610453-Benzyl-7-(4-bromo-2-chlorophenylamino)-8-chloro-[1,2,4]triazolo[4,3-a]pyridine-6-carboxylic acid methyl esterYield 33.4%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

Phenylacetyl chloride (152 μL, 1.148 mmol) was added to a solution of 4-(4-bromo-2-chlorophenylamino)-5-chloro-6-hydrazinonicotinic acid methyl ester (49) (0.233 g, 0.574 mmol) and triethylamine (160 μL, 1.148 mmol) in CH2Cl2 (5.7 mL) at 0° C. After warming to room temperature, an additional 75 μL phenylacetyl chloride was added. After 6 hours, the reaction mixture was concentrated and diluted with EtOAc. The organic layer was washed with water and brine, dried (Na2SO4) and concentrated. The residue (50b) was diluted with dichloroethylene (2 mL) and POCl3 (465 μL, 5.082 mmol) was added. After stirring at reflux for 12 hours, the reaction mixture was cooled to room temperature and concentrated. The residue was diluted with EtOAc and saturated NaHCO3 was added and the mixture stirred for 20 minutes. The resulting solid was collected by filtrate to give the desired product (51b) (97 mg, 30%).

Workup

  1. concentrationthe reaction mixture was concentrated
  2. additiondiluted with EtOAc
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. additionwas added
  7. temperatureat reflux for 12 hours
  8. temperaturethe reaction mixture was cooled to room temperature
  9. concentrationconcentrated
  10. additionThe residue was diluted with EtOAc and saturated NaHCO3
  11. additionwas added
  12. stirringthe mixture stirred for 20 minutes
  13. customThe resulting solid was collected by filtrate

Sources & evidence

ORD record
ord-382823a8a01f4526941ebb7d3f27f723
Source dataset
uspto-grants-2007_09
Patent number
US07271178B2

Reaction notes

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