Tetrabutylammonium Fluoride → 4-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-5-hydroxy-pentanoyl]-piperazine-1-carboxylic acid butyl ester

HRID 1970583Notes

Reaction equation

HRID 1970583 reaction equation
[CH2:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:67])[C@@H:15]([NH:37][C:38]([C:40]2[CH:44]=[C:43]([O:45][CH2:46][C:47]([N:49]3[CH2:53][CH2:52][CH2:51][C@H:50]3[C:54](=[O:60])[NH:55][CH:56]3[CH2:59][CH2:58][CH2:57]3)=[O:48])[N:42]([C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)[N:41]=2)=[O:39])[CH2:16][CH2:17][CH2:18][O:19][Si](C(C)(C)C)(C2C=CC=CC=2)C2C=CC=CC=2)[CH2:10][CH2:9]1)=[O:7])[CH2:2][CH2:3][CH3:4].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[CH2:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:67])[C@@H:15]([NH:37][C:38]([C:40]2[CH:44]=[C:43]([O:45][CH2:46][C:47]([N:49]3[CH2:53][CH2:52][CH2:51][C@H:50]3[C:54](=[O:60])[NH:55][CH:56]3[CH2:59][CH2:58][CH2:57]3)=[O:48])[N:42]([C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=3)[N:41]=2)=[O:39])[CH2:16][CH2:17][CH2:18][OH:19])[CH2:10][CH2:9]1)=[O:7])[CH2:2][CH2:3][CH3:4]

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 866504734-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-5-(tert-butyl-diphenyl-silanyloxy)-pentanoyl]-piperazine-1-carboxylic acid butyl ester

Product 1

HCID 668547594-[(S)-2-({5-[2-((S)-2-Cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-5-hydroxy-pentanoyl]-piperazine-1-carboxylic acid butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 400 mg 4-[(S)-5-(tert-Butyl-diphenyl-silanyloxy)-2-({5-[2-((S)-2-cyclobutylcarbamoyl-pyrrolidin-1-yl)-2-oxo-ethoxy]-1-phenyl-1H-pyrazole-3-carbonyl}-amino)-pentanoyl]-piperazine-1-carboxylic acid butyl ester in 40 ml THF were added 0.6 ml of TBAF (1 M in THF) and the mixture stirred at RT for 12 h. It was concentrated, the residue was dissolved in DCM and washed with water (3×). The solvent was removed under reduced pressure and the residue purified by preparative HPLC (C18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA). The fractions containing the product were lyophilized to yield the pure product.

Workup

  1. concentrationIt was concentrated
  2. dissolutionthe residue was dissolved in DCM
  3. washwashed with water (3×)
  4. customThe solvent was removed under reduced pressure
  5. customthe residue purified by preparative HPLC (
  6. washC18 reverse phase column, elution with a water/MeCN gradient with 0.1% TFA)
  7. additionThe fractions containing the product
  8. customto yield the pure product

Sources & evidence

ORD record
ord-297a4b65ba4a439bbafa49ac2a5dd577
Source dataset
uspto-grants-2013_04
Patent number
US08426420B2

Reaction notes

Loading…