Trifluoroacetic acid → 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

HRID 1469410Notes

Reaction equation

HRID 1469410 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.C(O)(C(F)(F)F)=O>ClCCl>[NH2:31][C@H:26]([CH2:25][C:24]#[C:23][C:20]1[CH:19]=[C:18]([C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][C:40]=2[CH3:46])[C:17]([N:16]([C:14](=[O:15])[C:13]([C:5]2[CH:4]=[C:3]([C:2]([F:50])([F:51])[F:1])[CH:8]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:6]=2)([CH3:48])[CH3:49])[CH3:47])=[CH:22][N:21]=1)[C:27]([O:29][CH3:30])=[O:28]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 57965578HCID 57965578, compound2×

Product 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-pentynoate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of methyl (2R)-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 12, 1 g, 1.382 mmol) in Dichloromethane (15 ml), TFA (5 ml, 64.9 mmol) was added and the reaction mixture was stirred for 1 h at r.t. The solvent and the excess of TFA were evaporated and the residue purified by SPE-SCX cartridge to obtain Intermediate 13. This residue was dissolved in Acetonitrile (14 ml) and Silver trifluoromethanesulfonate (0.036 g, 0.138 mmol) was added; the reaction mixture was stirred for 6 hours at 60° C. The solvent was evaporated and the residue was dissolved in DCM (15 ml) and the metal catalyst was filtered off. The organic solution was evaporated affording the title compound (800 mg, 1.283 mmol, 93% yield) as an orange solid. UPLC: Rt 0.95 min, m/z 624 [M+H+].

Workup

  1. customThe solvent and the excess of TFA were evaporated
  2. customthe residue purified by SPE-SCX cartridge

Sources & evidence

ORD record
ord-c1db29e07eb94fbd82ca2dcd95b8062a
Source dataset
uspto-grants-2015_04
Patent number
US09006271B2

Reaction notes

Loading…