Water → HCID 22346421, compound

HRID 897343Notes

Reaction equation

HRID 897343 reaction equation
[C:1]([N:4]1[CH:8]([C:9]2[N:18]=[C:17]([C:19]([O:21]C)=O)[C:16]([O:23]CC3C=CC(OC)=CC=3)=[C:15]3[C:10]=2[CH:11]=[CH:12][CH:13]=[N:14]3)[CH2:7][CH2:6][N:5]1[CH3:33])(=[O:3])[CH3:2].O.[C:35](O)([C:37]([F:40])(F)F)=O>C(#N)C>[C:1]([N:4]1[CH:8]([C:9]2[N:18]=[C:17]([C:19]([NH:14][CH2:15][C:10]3[CH:11]=[CH:35][C:37]([F:40])=[CH:8][CH:9]=3)=[O:21])[C:16]([OH:23])=[C:15]3[C:10]=2[CH:11]=[CH:12][CH:13]=[N:14]3)[CH2:7][CH2:6][N:5]1[CH3:33])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 22346322HCID 22346322, compound

Product 1

HCID 22346421HCID 22346421, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
120 °C

Procedure

A solution of the above acetylpyrazolidine (50 mg, Step 1), water (0.25 mL), and TFA (0.15 mL) in acetonitrile (5 mL) was stirred at room temperature for 6 hours. The resultant mixture was concentrated under vacuum. Residual water and TFA was removed by co-evaporation with additional acetonitrile (3×5 mL). Without further purification, the residual oil was treated with 4-fluorobenzylamine (0.2 mL) in a mixture of methanol (1 mL) and toluene (8 mL) in a sealed tube was heated in an oil bath at 120° C. for 2 hours. The product mixture was concentrated under vacuum. The residue was dissolved in DMSO, and subjected to HPLC purification on C-18 stationary phase eluted with water/acetonitrile/TFA mobile phase. Collection and lyophilization of appropriate fractions provided the title compound.

Workup

  1. concentrationThe resultant mixture was concentrated under vacuum
  2. customResidual water and TFA was removed by co-evaporation with additional acetonitrile (3×5 mL)
  3. customWithout further purification
  4. additionthe residual oil was treated with 4-fluorobenzylamine (0.2 mL) in a mixture of methanol (1 mL) and toluene (8 mL) in a sealed tube
  5. concentrationThe product mixture was concentrated under vacuum
  6. dissolutionThe residue was dissolved in DMSO
  7. customsubjected to HPLC purification on C-18 stationary phase
  8. washeluted with water/acetonitrile/TFA mobile phase
  9. customCollection and lyophilization of appropriate fractions

Sources & evidence

ORD record
ord-5061fef0435248c88cc827d80b927830
Source dataset
uspto-grants-2005_07
Patent number
US06921759B2

Reaction notes

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