Trifluoroacetic acid → 2-[(Phenylmethyl)oxy]-N-3-pyridinyl-5-{[(2S)-2-pyrrolidinylmethyl]oxy}benzamide

HRID 1623787Notes

Reaction equation

HRID 1623787 reaction equation
[C:1]1([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][C@@H:17]3[CH2:21][CH2:20][CH2:19][N:18]3C(OC(C)(C)C)=O)=[CH:11][C:10]=2[C:29]([NH:31][C:32]2[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=2)=[O:30])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.FC(F)(F)C(O)=O.C([O-])(O)=O.[Na+]>ClCCl>[C:1]1([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][C@@H:17]3[CH2:21][CH2:20][CH2:19][NH:18]3)=[CH:11][C:10]=2[C:29]([NH:31][C:32]2[CH:33]=[N:34][CH:35]=[CH:36][CH:37]=2)=[O:30])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 671073891,1-Dimethylethyl (2S)-2-[({4-[(phenylmethyl)oxy]-3-[(3-pyridinylamino)carbonyl]phenyl}oxy)methyl]-1-pyrrolidinecarboxylate

Product 1

HCID 671078412-[(Phenylmethyl)oxy]-N-3-pyridinyl-5-{[(2S)-2-pyrrolidinylmethyl]oxy}benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
25 °C

Procedure

To an ice-cooled solution of 1,1-dimethylethyl (2S)-2-[({4-[(phenylmethyl)oxy]-3-[(3-pyridinylamino)carbonyl]phenyl}oxy)methyl]-1-pyrrolidinecarboxylate (may be prepared as described in Description 74; 0.6 g, 1.19 mmol) in dichloromethane (15 ml) was added trifluoroacetic acid (2.0 ml, 26 mmol) dropwise. After stirred at 25° C. for 2 h, the pH of the solution was adjusted to 7-8 by adding aqueous NaHCO3 solution. The mixture was extracted with dichloromethane. The dichloromethane layer was washed with brine, dried over Na2SO4, and concentrated to obtain a crude product. The crude product was purified by prep-HPLC (Gilson GX-281, waters X-Bridge 5 μm, 100*19 mm; A: 0.04% NH3.H2O/water, B: CH3CN; 0-7 min, 35%-50%; 7-14 min, 95%; RT=7.0 min) to yield the title compound as a light yellow solid. 150 mg.

Workup

  1. extractionThe mixture was extracted with dichloromethane
  2. washThe dichloromethane layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customto obtain a crude product
  6. customThe crude product was purified by prep-HPLC (Gilson GX-281, waters X-Bridge 5 μm, 100*19 mm
  7. custom0-7 min, 35%-50%
  8. custom7-14 min, 95%

Sources & evidence

ORD record
ord-5f458890be294da09ffe7cb1984bd36d
Source dataset
uspto-grants-2014_07
Patent number
US08778939B2

Reaction notes

Loading…