Potassium Carbonate → HCID 23573180, compound

HRID 1825253Notes

Reaction equation

HRID 1825253 reaction equation
[CH2:1]([O:8][C:9](=[O:27])[CH:10]([NH:15][CH:16]([C:23]([O:25][CH3:26])=[O:24])[CH2:17][C:18]1[CH:22]=[CH:21][NH:20][N:19]=1)[CH2:11][CH:12]([CH3:14])[CH3:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[Cl:34][C:35]1[CH:36]=[C:37]([CH:40]=[C:41]([Cl:43])[CH:42]=1)[CH2:38]Br>C(#N)C.C(OCC)(=O)C.O.CCCCCC>[CH2:1]([O:8][C:9](=[O:27])[CH:10]([NH:15][CH:16]([C:23]([O:25][CH3:26])=[O:24])[CH2:17][C:18]1[N:19]([CH2:38][C:37]2[CH:36]=[C:35]([Cl:34])[CH:42]=[C:41]([Cl:43])[CH:40]=2)[N:20]=[CH:21][CH:22]=1)[CH2:11][CH:12]([CH3:13])[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 125839781-(Bromomethyl)-3,5-dichlorobenzeneHCID 178499995HCID 178499995, compound

Product 1

HCID 23573180HCID 23573180, compound

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
50 °C

Procedure

The pyrazole 53-6 (300 mg, 0.803 mmol) was dissolved in acetonitrile (8 mL). K2CO3 (212 mg, 1.61 mmol) and 3,5-dichlorobenzyl bromide (231 mg, 0.964 mmol) were added, and the resulting mixture was warmed to 50° C. and stirred overnight. The reaction mixture was cooled to room temperature and diluted with ethyl acetate and water. The aqueous phase was extracted with ethyl acetate. Combined organic phases were washed with water and brine, dried over Na2SO4, filtered, and concentrated to give a yellow oil. Purification by column chromatography (ISCO chromatography system, SiO2, elution with 10 to 20% ethyl acetate in hexane) provided two sets of fractions. A pale yellow oil (152 mg, Rf=0.5, 40% ethyl acetate in hexane) provided a 1H NMR consistent with the previously isolated 53-7a. Another yellow oil (38 mg, mixture of spots by TLC) provided a 1H NMR consistent with a mixture of compounds. Further purification of this material by column chromatography (ISCO chromatography system, SiO2, elution with 10 to 20% ethyl acetate in hexane) provided a colorless oil (23 mg, Rf=0.58, 40% ethyl acetate in hexane) consistent with 2-{2-[2-(3,5 dichloro-benzyl)-2H-pyrazol-3-yl]-1-methoxycarbonyl-ethylamino}-4-methyl-pentanoic acid benzyl ester 53-7b. The proposed structure was supported by 2D NMR methods (NOESY, HMBC and HMQC).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe aqueous phase was extracted with ethyl acetate
  3. washCombined organic phases were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a yellow oil
  8. customPurification
  9. washby column chromatography (ISCO chromatography system, SiO2, elution with 10 to 20% ethyl acetate in hexane)
  10. customprovided two sets of fractions
  11. custompreviously isolated 53-7a
  12. additionAnother yellow oil (38 mg, mixture of spots by TLC)
  13. customprovided a 1H NMR
  14. additionconsistent with a mixture of compounds
  15. customFurther purification of this material
  16. washby column chromatography (ISCO chromatography system, SiO2, elution with 10 to 20% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-33e7180e89ee4edb97ef7a3057a2d412
Source dataset
uspto-grants-2006_05
Patent number
US07045532B2

Reaction notes

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