p-Toluenesulfonic acid → HCID 11453842, compound

HRID 133475

Reaction equation

HRID 133475 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C:19]#[N:20])[CH:14]=2)[C@@H:10]([NH2:12])[CH3:11])=[CH:4][CH:3]=1.[C:21]1([C:27](=O)[CH2:28][N:29]2[CH:33]=[CH:32][CH:31]=[N:30]2)[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@@H:9]([C:13]2[CH:14]=[C:15]([CH:16]=[CH:17][CH:18]=2)[C:19]#[N:20])[C@@H:10]([NH:12][CH:27]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH2:28][N:29]2[CH:33]=[CH:32][CH:31]=[N:30]2)[CH3:11])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 27663751-Phenyl-2-(1H-pyrazol-1-yl)ethanoneHCID 115872963-((2S,3S)-3-amino-1-(4-chlorophenyl)butan-2-yl)benzonitrile

Product 1

HCID 11453842HCID 11453842, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 80 mg (0.28 mmol) of 3-(4-chlorophenyl)-2(S)(3-cyanophenyl)-1(S)-methyl-propylamine in 1.5 mL of toluene, 60 mg of 1-phenyl-2(1H-pyrazol-1-yl)ethanone and 5 mg of TsOH were added. Powdered 4A molecular sieves (˜300 mg) were added to the reaction and it was heated to reflux for 5 hr. The mixture was allowed to cool overnight, filtered and the solid washed with EtOAc. The filtrate was concentrated and the residue was dissolved in 1.5 mL of THF, 0.1 mL of acetic acid. This solution was treated with 20 mg of NaCNBH3 for 1.5 hr. The reaction was diluted with EtOAc, washed with saturated NaHCO3, brine, dried and concentrated. The residue was purified on a prep TLC plate using 50% EtOAC-hexane as eluant to isolate of the higher Rf isomer, 3-(1(S)-(4-chlorobenzyl)-2(S)-((1-phenyl-2-(1H-pyrazol-1-yl)ethyl)amino)propyl)benzonitrile (Diastereomer A) LC-MS: m/e=455 (M+1), 457 (M+3) (3.16 min). and the lower Rf isomer, 3-(1(S)-(4-chlorobenzyl)-2(S)-(1-phenyl-2-(1H-pyrazol-1-yl)ethyl)amino)propyl)benzonitrile (Diastereomer B) LC-MS: m/e=455 (M+1), 457 (M+3) (3.12 min).

Workup

  1. additionwere added to the reaction and it
  2. temperaturewas heated
  3. temperatureto reflux for 5 hr
  4. temperatureto cool overnight
  5. filtrationfiltered
  6. washthe solid washed with EtOAc
  7. concentrationThe filtrate was concentrated
  8. dissolutionthe residue was dissolved in 1.5 mL of THF
  9. additionThis solution was treated with 20 mg of NaCNBH3 for 1.5 hr
  10. additionThe reaction was diluted with EtOAc
  11. washwashed with saturated NaHCO3, brine
  12. customdried
  13. concentrationconcentrated
  14. customThe residue was purified on a prep TLC plate

Sources & evidence

ORD record
ord-e02f32f8dd1a4bdeb756e6048ee24ddb
Source dataset
uspto-grants-2008_06
Patent number
US07390835B2

Linked notes

Loading…