Pyrazole-3,5-dicarboxylic acid → HCID 71074190, compound

HRID 1485840Notes

Reaction equation

HRID 1485840 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C@H:4]([OH:15])[C@H:5]([NH2:14])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[Cl:13].CN(C(ON1N=N[C:27]2C=CC=N[C:26]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:41]1[C:45]([C:46]([OH:48])=[O:47])=[CH:44][C:43]([C:49]([OH:51])=O)=[N:42]1.[CH3:52]CN(C(C)C)C(C)C>CN(C=O)C.CCOC(C)=O>[CH2:26]([O:48][C:46]([C:45]1[NH:41][N:42]=[C:43]([C:49](=[O:51])[NH:14][C@H:5]([CH2:6][C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[Cl:13])[C@H:4]([C:3]([O:2][CH2:1][CH3:52])=[O:16])[OH:15])[CH:44]=1)=[O:47])[CH3:27]

Participants

7

Reactant 4

HCID 76559Pyrazole-3,5-dicarboxylic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 71073768HCID 71073768, compound

Product 1

HCID 71074190HCID 71074190, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(2R,3R)-3-Amino-4-(2-chloro-phenyl)-2-hydroxy-butyric acid methyl ester (735 mg, 3.0 mmol, 1.0 eq.), HATU (1.2 g, 3.2 mmol, 1.0 eq.), and 3,5-pyrazoledicarboxylic acid (0.5 g, 3.2 mmol, 1.0 eq.) were combined in DMF (5 mL) and stirred. DIPEA (2 mL, 4.0 eq.) was added and the mixture was stirred for 1 hour at room temperature. EtOAc (200 mL) was added and the mixture was washed with 1N HCl (100 mL), NaHCO3 ((100 mL), and saturated aqueous NaCl (100 mL). The organic layer was retained and dried over anhydrous MgSO4 for 10 minutes prior to filtration. The product was then vacuumed to dryness. The product was dissolved in absolute EtOH (100 mL) and concentrated HCl (1 mL) was added, and the mixture refluxed for 5 hours. EtOAc (200 mL) was added and the mixture was washed with 1N HCl (100 mL) followed by NaHCO3 (100 mL) and then saturated aqueous NaCl (100 mL). The organic layer was retained and dried over anhydrous MgSO4 for 10 minutes prior to filtration and evacuation to dryness to yield the title compound (750 mg).

Workup

  1. stirringthe mixture was stirred for 1 hour at room temperature
  2. washthe mixture was washed with 1N HCl (100 mL), NaHCO3 ((100 mL), and saturated aqueous NaCl (100 mL)
  3. dry with materialdried over anhydrous MgSO4 for 10 minutes
  4. filtrationto filtration
  5. dissolutionThe product was dissolved in absolute EtOH (100 mL)
  6. additionconcentrated HCl (1 mL) was added
  7. temperaturethe mixture refluxed for 5 hours
  8. additionEtOAc (200 mL) was added
  9. washthe mixture was washed with 1N HCl (100 mL)
  10. dry with materialdried over anhydrous MgSO4 for 10 minutes
  11. filtrationto filtration and evacuation to dryness

Sources & evidence

ORD record
ord-c2f8d826559c4ca598bd5a3fe92e6da1
Source dataset
uspto-grants-2016_08
Patent number
US09422245B2

Reaction notes

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