Pyridine → HCID 19783054, compound

HRID 257325Notes

Reaction equation

HRID 257325 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[C:12]([Cl:13])=[CH:11][C:10]([C:14]([F:17])([F:16])[F:15])=[C:9]([NH:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:8]=2)[N:5]=[CH:4][C:3]=1[C:26]#[N:27].N1C=CC=CC=1.[C:34](Cl)(=[O:37])[CH2:35][CH3:36].C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.C(O)C.O>[Cl:13][C:12]1[C:7]([N:6]2[C:2]([NH:1][C:34]([CH2:35][CH3:36])=[O:37])=[C:3]([C:26]#[N:27])[CH:4]=[N:5]2)=[N:8][C:9]([NH:18][CH2:19][C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)=[C:10]([C:14]([F:16])([F:15])[F:17])[CH:11]=1

Participants

8

Reactant 4

HCID 1049PyridineHCID 11430Potassium CarbonateHCID 62324Propionyl chlorideHCID 19783052HCID 19783052, compound

Product 1

HCID 19783054HCID 19783054, compoundYield 113.6%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

A stirred solution of 0.5 gram (0.001 mole) of 5-amino-1-(3-chloro-5-trifluoromethyl-6-phenylmethylaminopyridin-2-yl)-4-cyanopyrazole and 1.0 gram (0.013 mole) of pyridine in 25 mL of methylene chloride was cooled to -10° C. A solution of 1.2 grams (0.013 mole) of propionyl chloride in 10 mL of methylene chloride was added dropwise. After completion of the addition, the reaction mixture was allowed to warm to room temperature and then was heated at reflux for approximately 19 hours. The reaction mixture was cooled and evaporated under reduced pressure, leaving an oil. This oil was partitioned between diethyl ether and water. The organic phase was washed in succession with water, dilute hydrochloric acid, and water. The washed organic phase was evaporated under reduced pressure, leaving a residue. This residue was dissolved in 13 mL of ethanol and 13 mL of water. The resultant mixture was stirred and heated at reflux. Potassium carbonate (0.20 gram, 0.0014 mole) was added, and the mixture was stirred and heated at reflux for approximately 15 minutes. The solvents were removed by distillation under reduced pressure, leaving a waxy solid. This solid was purified by crystallization from ethanol and water to yield 0.51 gram of 1-(3-chloro-5-trifluoromethyl-6-phenylmethylaminopyridin-2-yl)-4-cyano-5-ethylcarbonylaminopyrazole, m.p. 139°-142° C. (Compound 53 of Table 1). The rmr spectrum was consistent with the proposed structure.

Workup

  1. additionAfter completion of the addition
  2. temperaturewas heated
  3. temperatureat reflux for approximately 19 hours
  4. temperatureThe reaction mixture was cooled
  5. customevaporated under reduced pressure
  6. customleaving an oil
  7. customThis oil was partitioned between diethyl ether and water
  8. washThe organic phase was washed in succession with water, dilute hydrochloric acid, and water
  9. customThe washed organic phase was evaporated under reduced pressure
  10. customleaving a residue
  11. temperatureheated
  12. temperatureat reflux
  13. temperatureheated
  14. temperatureat reflux for approximately 15 minutes
  15. customThe solvents were removed by distillation under reduced pressure
  16. customleaving a waxy solid
  17. customThis solid was purified by crystallization from ethanol and water

Sources & evidence

ORD record
ord-44b718cb9bf047299ade2018819d5a07
Source dataset
uspto-grants-1993_11
Patent number
US05262382

Reaction notes

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