2-Dimethylaminopyridine → rac-(2R,3R,4R,5s)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (3-methanesulfonylamino-propyl)-amide

HRID 1807214Notes

Reaction equation

HRID 1807214 reaction equation
[NH2:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([CH:8]1[CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)[C:11]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)([C:20]#[N:21])[CH:10]([CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[NH:9]1)=[O:7].[CH3:34][S:35](Cl)(=[O:37])=[O:36].CN(C1C=CC=CN=1)C>C(Cl)Cl>[CH3:34][S:35]([NH:1][CH2:2][CH2:3][CH2:4][NH:5][C:6]([CH:8]1[CH:12]([C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)[C:11]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)([C:20]#[N:21])[CH:10]([CH2:29][C:30]([CH3:33])([CH3:32])[CH3:31])[NH:9]1)=[O:7])(=[O:37])=[O:36]

Participants

5

Reactant 3

HCID 218852-DimethylaminopyridineHCID 31297Methanesulfonyl chlorideHCID 75095855Rac-(2r,3r,4r,5s)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid(3-amino-propyl)-amide

Product 1

HCID 72243932rac-(2R,3R,4R,5s)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (3-methanesulfonylamino-propyl)-amideYield 82.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of rac (2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (3-amino-propyl)-amide (120 mg, 0.24 mmol), methane sulfonyl chloride (49 μL, 0.6 mmol) and dimethylaminopyridine (97.6 mg, 0.8 mmol) in CH2Cl2 (8 mL) was stirred for 5 h at rt. The mixture was then extracted with NaHCO3(s), water and the organic layer dried with MgSO4, filtered and the solvent was evaporated under reduced pressure. diluted with CH2Cl2 and washed with water, brine. The organic phase was separated, filtered and dried over Na2SO4. The mixture was then purified by reverse phase chromatography (20-95% of ACN/water) to give rac-(2R,3R,4R,5S)-3-(3-chloro-phenyl)-4-(4-chloro-phenyl)-4-cyano-5-(2,2-dimethyl-propyl)-pyrrolidine-2-carboxylic acid (3-methanesulfonylamino-propyl)-amide (112.1 mg, 80.5%) as an off-white powder. HRMS (ES+) m/z Calcd for C27H34Cl2N4O3S+H [(M+H)+]: 565.1802. found: 565.1800.

Workup

  1. extractionThe mixture was then extracted with NaHCO3(s), water
  2. dry with materialthe organic layer dried with MgSO4
  3. filtrationfiltered
  4. customthe solvent was evaporated under reduced pressure
  5. additiondiluted with CH2Cl2
  6. washwashed with water, brine
  7. customThe organic phase was separated
  8. filtrationfiltered
  9. dry with materialdried over Na2SO4
  10. customThe mixture was then purified by reverse phase chromatography (20-95% of ACN/water)

Sources & evidence

ORD record
ord-edb5743748c44d9f883a77599ce2b825
Source dataset
uspto-grants-2013_01
Patent number
US08354444B2

Reaction notes

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