Sodium Hydroxide → Trifluoroacetic acid

HRID 882572Notes

Reaction equation

HRID 882572 reaction equation
[NH2:1][C@H:2]([CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]([F:17])([F:16])[F:15])[CH2:3][C:4]([OH:6])=[O:5].[NH:18]1[C:22]([C:23]([OH:25])=[O:24])=[CH:21][C:20]([C:26](O)=[O:27])=[N:19]1.CN(C([O:36]N1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[OH-:62].[Na+]>CN(C=O)C.CO.CC(O)=O>[C:4]([CH2:3][C@H:2]([NH:1][C:26]([C:20]1[CH:21]=[C:22]([C:23]([OH:25])=[O:24])[NH:18][N:19]=1)=[O:27])[CH2:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:14]([F:15])([F:16])[F:17])([OH:6])=[O:5].[C:9]([OH:36])([C:14]([F:17])([F:16])[F:15])=[O:62]

Participants

10

Reactant 5

HCID 14798Sodium HydroxideHCID 76559Pyrazole-3,5-dicarboxylic acidHCID 81531DiisopropylethylamineHCID 5706704HCID 5706704, compoundHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Product 2

HCID 6422Trifluoroacetic acidYield 97%HCID 710742985-[(R)-2-Carboxy-1-(2-trifluoromethylbenzyl)-ethylcarbamoyl]-2H-pyrazole-3-carboxylic Acid

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Procedure

(R)-3-Amino-4-(2-trifluoromethyl-phenyl)-butyric acid (63 mg, 260 μmol, 1.0 eq.), 3,5-pyrazoledicarboxylic acid (40 mg, 0.2 mmol, 1.0 eq.), and HATU (97 mg, 260 μmol, 1.0 eq.) were dissolved in DMF (5 mL) and stirred. DIPEA (200 μL, 4.0 eq.) was added and the resulting mixture was stirred at room temperature for 1 hour. The product was then vacuumed to dryness. This crude product was dissolved in MeOH (3 mL), and 10N NaOH (250 μL) was added. The resulting mixture was stirred at 60° C. for 1 hour. Glacial AcOH (250 μL) was added and the mixture was then vacuumed to dryness. The product was then purified by preparative HPLC to yield the title compound as a TFA salt (26.4 mg, 97% purity). MS m/z [M+H]+ calc'd for C16H14F3N3O5, 386.09. found 386.0.

Workup

  1. stirringthe resulting mixture was stirred at room temperature for 1 hour
  2. stirringThe resulting mixture was stirred at 60° C. for 1 hour
  3. customThe product was then purified by preparative HPLC

Sources & evidence

ORD record
ord-e7ff79c19f124585a7ea2270a835b04b
Source dataset
uspto-grants-2015_03
Patent number
US08993752B2

Reaction notes

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