methyl (2R)-2-amino-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-4-pentynoate → methyl (2R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-3,4-dihydro-2H-pyrrole-2-carboxylate

HRID 69538

Reaction equation

HRID 69538 reaction equation
[NH2:1][C@H:2]([CH2:7][C:8]#[C:9][C:10]1[CH:15]=[C:14]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=2[CH3:23])[C:13]([N:24]([C:26](=[O:44])[C:27]([C:30]2[CH:35]=[C:34]([C:36]([F:39])([F:38])[F:37])[CH:33]=[C:32]([C:40]([F:43])([F:42])[F:41])[CH:31]=2)([CH3:29])[CH3:28])[CH3:25])=[CH:12][N:11]=1)[C:3]([O:5][CH3:6])=[O:4]>C(#N)C.FC(F)(F)S([O-])(=O)=O.[Ag+]>[F:37][C:36]([F:38])([F:39])[C:34]1[CH:35]=[C:30]([C:27]([CH3:28])([CH3:29])[C:26]([N:24]([CH3:25])[C:13]2[C:14]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][C:17]=3[CH3:23])=[CH:15][C:10]([C:9]3[CH2:8][CH2:7][C@H:2]([C:3]([O:5][CH3:6])=[O:4])[N:1]=3)=[N:11][CH:12]=2)=[O:44])[CH:31]=[C:32]([C:40]([F:41])([F:43])[F:42])[CH:33]=1

Participants

4

Reactant 1

HCID 57965568methyl (2R)-2-amino-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-4-pentynoate2×

Product 1

HCID 57965574methyl (2R)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-3,4-dihydro-2H-pyrrole-2-carboxylateYield 118.8%

Reagents, catalysts & solvents 2

HCID 76223Silver(I) trifluoromethanesulfonateCatalystHCID 6342AcetonitrileSolvent

Procedure

Silver trifluoromethanesulfonate (0.381 g, 1.483 mmol) was added portionwise to a solution of methyl (2R)-2-amino-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-4-pentynoate (Intermediate 13, 1.85 g, 2.97 mmol) in anhydrous Acetonitrile (25 ml) and the resulting reaction mixture was stirred at room temperature overnight. Volatiles were evaporated under vacuo at room temperature. The residue was taken-up in dichloromethane and filtered through a plug of celite to afford 2.2 g of the title compound as a brown solid (the material contained some residual acetonitrile, therefore overall recovered amount was higher than the theoretical amount).

Workup

  1. customthe resulting reaction mixture
  2. customVolatiles were evaporated under vacuo at room temperature
  3. filtrationfiltered through a plug of celite

Sources & evidence

ORD record
ord-0cb35fc63e4340b2ac368e0ac56b75f9
Source dataset
uspto-grants-2014_09
Patent number
US08822504B2

Linked notes

Loading…