Pyrazole-3,5-dicarboxylic acid → 5-[(R)-2-Biphenyl-4-yl-1-(1-carboxy-cyclopropylmethyl)-ethylcarbamoyl]-2H-pyrazole-3-carboxylic acid

HRID 2096116Notes

Reaction equation

HRID 2096116 reaction equation
[NH:1]1[C:5]([C:6]([OH:8])=O)=[CH:4][C:3]([C:9]([OH:11])=[O:10])=[N:2]1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:45][C@H:46]([CH2:54][C:55]1[CH:60]=[CH:59][C:58]([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)=[CH:57][CH:56]=1)[CH2:47][C:48]1([C:51]([OH:53])=[O:52])[CH2:50][CH2:49]1>C(Cl)Cl>[C:58]1([C:61]2[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=2)[CH:57]=[CH:56][C:55]([CH2:54][C@@H:46]([NH:45][C:6]([C:5]2[CH:4]=[C:3]([C:9]([OH:11])=[O:10])[NH:2][N:1]=2)=[O:8])[CH2:47][C:48]2([C:51]([OH:53])=[O:52])[CH2:50][CH2:49]2)=[CH:60][CH:59]=1

Participants

6

Reactant 4

HCID 76559Pyrazole-3,5-dicarboxylic acidHCID 81531Diisopropylethylamine2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 681808381-((R)-2-Amino-3-biphenyl-4-yl-propyl)-cyclopropanecarboxylic acid

Product 1

HCID 681810015-[(R)-2-Biphenyl-4-yl-1-(1-carboxy-cyclopropylmethyl)-ethylcarbamoyl]-2H-pyrazole-3-carboxylic acidYield 93%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

3,5-Pyrazoledicarboxylic acid (35.2 mg, 226 μmol, 1.0 eq.), DIPEA (126 μL) and HATU (85.9 mg, 226 μmol, 1.0 eq.) and DCM (5 mL) were combined and stirred for 5 minutes at room temperature. 1-((R)-2-Amino-3-biphenyl-4-yl-propyl)-cyclopropanecarboxylic acid (86.7 mg, 294 μmol, 2.3 eq,) and DIPEA (0.5 mL) in DCM (5 mL) was added, and the resulting mixture was stirred for 1 hour. The reaction was quenched with saturated aqueous NH4Cl and the product was extracted with DCM, dried and evaporated. The resulting product was combined with AcOH (1.5 mL) and purified with preparative HPLC to yield the title compound (21.4 mg; 93% purity). MS m/z [M+H]+ calc'd for C24H23N3O5, 434.16; found 433.5.

Workup

  1. stirringthe resulting mixture was stirred for 1 hour
  2. customThe reaction was quenched with saturated aqueous NH4Cl
  3. extractionthe product was extracted with DCM
  4. customdried
  5. customevaporated
  6. custompurified with preparative HPLC

Sources & evidence

ORD record
ord-2858673348254a5fa0c462c225cecb95
Source dataset
uspto-grants-2013_05
Patent number
US08449890B2

Reaction notes

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