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

HRID 84211Notes

Reaction equation

HRID 84211 reaction equation
C([O:5][C:6]([C:8]1([CH2:11][C@H:12]([NH:26]C(OC(C)(C)C)=O)[CH2:13][C:14]2[CH:19]=[CH:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])(C)(C)C.Cl.[NH:35]1[C:39]([C:40]([OH:42])=[O:41])=[CH:38][C:37]([C:43]([OH:45])=O)=[N:36]1.CCN=C=NCCCN(C)C.[CH:57]1[CH:58]=CC2N(O)N=N[C:61]=2[CH:62]=1>O1CCOCC1.CN(C=O)C.C(O)CCC>[C:17]1([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH:18]=[CH:19][C:14]([CH2:13][C@@H:12]([NH:26][C:43]([C:37]2[NH:36][N:35]=[C:39]([C:40]([OH:42])=[O:41])[CH:38]=2)=[O:45])[CH2:11][C:8]2([C:6]([O:5][CH2:58][CH2:57][CH2:62][CH3:61])=[O:7])[CH2:10][CH2:9]2)=[CH:15][CH:16]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 76559Pyrazole-3,5-dicarboxylic acidHCID 681808691-((R)-3-Biphenyl-4-yl-2-t-butoxycarbonylaminopropyl)cyclopropanecarboxylic acid t-butyl ester

Product 1

HCID 1784507415-[(R)-1-Biphenyl-4-ylmethyl-2-(1-butoxycarbonyl-cyclopropyl)-ethylcarbamoyl]-1H-pyrazole-3-carboxylic acidYield 95%

Reagents, catalysts & solvents 3

HCID 2631-ButanolSolventHCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

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.

Workup

  1. additionTo this was added
  2. stirringstirred for 5 minutes at room temperature
  3. stirringThe resulting mixture was stirred for 30 minutes
  4. customThe reaction was then quenched with ACOH
  5. customthe product was purified by preparative HPLC

Sources & evidence

ORD record
ord-4ea5be69091d4e85abc951f141d1a129
Source dataset
uspto-grants-2014_09
Patent number
US08846913B2

Reaction notes

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