Reaction #171393

Reaction equation

1-((R)-3-Biphenyl-4-yl-2-t -butoxycarbonylaminopropyl)cyclopropanecarboxylic acid t-butyl ester

HCl

3,5-pyrazoledicarboxylic acid

EDCI

HOBt

→

title compound

Yield 95.0%

5-[(R)-1-Biphenyl-4-ylmethyl-2-(1-butoxycarbonyl -cyclopropyl)-ethylcarbamoyl]-1H-pyrazole-3-carboxylic acid

Yield 95.0%

Solvents

1,4-dioxane

DMF

1-butanol

Conditions

Workup

1. 1
   workup.ADDITIONTo this was added
2. 2
   workup.STIRRINGstirred for 5 minutes at room temperature
3. 3
   workup.STIRRINGThe resulting mixture was stirred for 30 minutes
4. 4
   OtherThe reaction was then quenched with ACOH
5. 5
   Otherthe product was purified by preparative HPLC

Procedure

1-((R)-3-Biphenyl-4-yl-2-t -butoxycarbonylaminopropyl)cyclopropanecarboxylic acid t-butyl ester (1.0 g, 2.2 mmol, 1.0 eq.), 1-butanol (5 mL) and 4 M of HCl in 1,4-dioxane (2 mL) were combined and stirred at 65° C. overnight. To this was added a mixture of 3,5-pyrazoledicarboxylic acid (34.6 mg, 221 mmol, 1.0 eq.), EDCI (39.2 mL, 221 mmol, 1.0 eq.) and HOBt (29.9 mg, 221 mmol, 1.0 eq.) that had been combined in DMF (0.2 mL) and stirred for 5 minutes at room temperature. The resulting mixture was stirred for 30 minutes. The reaction was then quenched with ACOH and the product was purified by preparative HPLC and lyophilized to yield the title compound (29 mg, 95% purity). MS m/z [M+H]+ calc'd for C28H31N3O5, 490.23; Found 490.6.

Source