Hexamethyldisilazane → Chloro-4-{[(3S)-1-(1-methylethyl)-5-oxo-3-pyrrolidinyl]amino}benzonitrile

HRID 1160405Notes

Reaction equation

HRID 1160405 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]([NH:11][C@H:12]([CH2:17][NH:18][CH:19]([CH3:21])[CH3:20])[CH2:13][C:14](O)=[O:15])[CH:6]=[CH:7][C:8]=1[C:9]#[N:10].C[Si](N[Si](C)(C)C)(C)C>CC#N.O>[Cl:2][C:3]1[CH:4]=[C:5]([NH:11][C@H:12]2[CH2:13][C:14](=[O:15])[N:18]([CH:19]([CH3:21])[CH3:20])[CH2:17]2)[CH:6]=[CH:7][C:8]=1[C:9]#[N:10]

Participants

5

Reactant 2

HCID 13838HexamethyldisilazaneHCID 68484641(3S)-3-[(3-chloro-4-cyanophenyl)amino]-4-[(1-methylethyl)amino]butanoic acid hydrochloride

Product 1

HCID 59516187Chloro-4-{[(3S)-1-(1-methylethyl)-5-oxo-3-pyrrolidinyl]amino}benzonitrileYield 49%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

The crude (3S)-3-[(3-chloro-4-cyanophenyl)amino]-4-[(1-methylethyl)amino]butanoic acid hydrochloride was dissolved in MeCN (20 mL) and treated with HMDS (4 mL) and the reaction was stirred at 60° C. for 15 h. After cooled down, the reaction was diluted with H2O and extracted with Et2O (2×). The combined organic extracts were washed with H2O (2×), dried over Na2SO4, filtered, concentrated, and purified by silica gel chromatography with 25% EtOAC in hexane grading to 100% EtOAc in hexane to yield the titled product (0.13 g, 49%). LC-MS (ES) m/e 277.9 (M+H)+.

Workup

  1. temperatureAfter cooled down
  2. extractionextracted with Et2O (2×)
  3. washThe combined organic extracts were washed with H2O (2×)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custompurified by silica gel chromatography with 25% EtOAC in hexane grading to 100% EtOAc in hexane

Sources & evidence

ORD record
ord-8298a58160724831b08b5baba5960f48
Source dataset
uspto-grants-2010_10
Patent number
US07816395B2

Reaction notes

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