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

HRID 2096117Notes

Reaction equation

HRID 2096117 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 μg, 221 μmol, 1.0 eq.), EDCI (39.2 μL, 221 μmol, 1.0 eq.) and HOBt (29.9 mg, 221 μmol, 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-cfe04a8d595948f4b277a387aeda295b
Source dataset
uspto-grants-2013_05
Patent number
US08449890B2

Reaction notes

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