Dichloromethane → methyl (2S)-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 1798974Notes

Reaction equation

HRID 1798974 reaction equation
[F:1][C:2]([F:51])([F:50])[C:3]1[CH:4]=[C:5]([C:13]([CH3:49])([CH3:48])[C:14]([N:16]([CH3:47])[C:17]2[C:18]([C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][C:40]=3[CH3:46])=[CH:19][C:20]([C:23]#[C:24][CH2:25][C@H:26]([NH:31]C(OC(C)(C)C)=O)[C:27]([O:29][CH3:30])=[O:28])=[N:21][CH:22]=2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.ClCCl>C(S([O-])(=O)=O)(F)(F)F.[Ag+]>[F:50][C:2]([F:1])([F:51])[C:3]1[CH:4]=[C:5]([C:13]([CH3:49])([CH3:48])[C:14]([N:16]([CH3:47])[C:17]2[C:18]([C:39]3[CH:44]=[CH:43][C:42]([F:45])=[CH:41][C:40]=3[CH3:46])=[CH:19][C:20]([C:23]3[CH2:24][CH2:25][C@@H:26]([C:27]([O:29][CH3:30])=[O:28])[N:31]=3)=[N:21][CH:22]=2)=[O:15])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

4

Reactant 2

HCID 6344DichloromethaneHCID 57965572methyl (2S)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-pentynoate2×

Product 1

HCID 57965548methyl (2S)-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 100%

Reagents, catalysts & solvents 1

HCID 76223Silver(I) trifluoromethanesulfonateCatalyst

Procedure

To a solution of methyl (2S)-5-[5-[{2-[3,5-bis(trifluoromethyl)phenyl]-2-methylpropanoyl}(methyl)amino]-4-(4-fluoro-2-methylphenyl)-2-pyridinyl]-2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-pentynoate (Intermediate 2, 750 mg, 1.036 mmol) in dry Dichloromethane (10 ml) trifluoroacetic acid (3 ml, 1.036 mmol) was added and the reaction mixture was stirred for 1 h at r.t. The solvent and the excess of trifluoroacetic acid were removed under vacuum and the residue was purified by SPE-SCX cartridge (10 g). The obtained light yellow solid was dissolved in acetonitrile (10 ml) and AgOTf (26.6 mg, 0.104 mmol) was added and the reaction mixture was stirred overnight at r.t. The solvent was evaporated and the residue was dissolved in ethyl acetate and filtered. The organic layer was collected and evaporated to afford the title compound (645 mg, 1.034 mmol, 100% yield) as a pale yellow solid. UPLC: Rt 0.95 min, m/z 624 [M+H]+.

Workup

  1. customThe solvent and the excess of trifluoroacetic acid were removed under vacuum
  2. customthe residue was purified by SPE-SCX cartridge (10 g)
  3. dissolutionThe obtained light yellow solid was dissolved in acetonitrile (10 ml)
  4. stirringthe reaction mixture was stirred overnight at r.t
  5. customThe solvent was evaporated
  6. dissolutionthe residue was dissolved in ethyl acetate
  7. filtrationfiltered
  8. customThe organic layer was collected
  9. customevaporated

Sources & evidence

ORD record
ord-71c23adce829468ab37dfdc3599bc173
Source dataset
uspto-grants-2013_01
Patent number
US08344005B2

Reaction notes

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