1-(4-Fluorophenyl)-2-methyl-2-aminopropane → (2S,5R)-5-ethynyl-1-{N-(2-(4-fluorophenyl)-1,1-dimethylethyl)glycyl}pyrrolidine-2-carbonitrile

HRID 475388Notes

Reaction equation

HRID 475388 reaction equation
Cl[CH2:2][C:3]([N:5]1[C@@H:9]([C:10]#[CH:11])[CH2:8][CH2:7][C@H:6]1[C:12]#[N:13])=[O:4].[F:14][C:15]1[CH:20]=[CH:19][C:18]([CH2:21][C:22]([NH2:25])([CH3:24])[CH3:23])=[CH:17][CH:16]=1>C(#N)C>[C:10]([C@@H:9]1[N:5]([C:3](=[O:4])[CH2:2][NH:25][C:22]([CH3:24])([CH3:23])[CH2:21][C:18]2[CH:19]=[CH:20][C:15]([F:14])=[CH:16][CH:17]=2)[C@H:6]([C:12]#[N:13])[CH2:7][CH2:8]1)#[CH:11]

Participants

4

Reactant 2

HCID 5184711-(4-Fluorophenyl)-2-methyl-2-aminopropaneHCID 16090854(2S,5R)-1-(2-chloroacetyl)-5-ethynylpyrrolidine-2-carbonitrile

Product 1

HCID 46851168(2S,5R)-5-ethynyl-1-{N-(2-(4-fluorophenyl)-1,1-dimethylethyl)glycyl}pyrrolidine-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of (2S,5R)-1-(chloroacetyl)-5-ethynylpyrrolidine-2-carbonitrile (0.05 g, 0.25 mmol, Example 8D) in acetonitrile (3 mL) at room temperature under nitrogen was added 1-(4-fluorophenyl)-2-methyl-2-propylamine (0.09 g, 0.508 mmol). The reaction mixture was stirred for two days and then concentrated under reduced pressure. The residue was flash chromatographed with 1-2% MeOH/CH2Cl2 to provide the desired compound as a white powder. MS (DCI) m/z 328 (M+H)+; 1H NMR (300 MHz, DMSO-d6) δ 2.01-2.04 (2H, m), 2.05 (2H, s), 2.07 (2H, s), 3.03 (1H, m), 3.04 (6H, s), 3.5-4.57 (2H, m), 4.57-4.58 (1H, m), 4.58-5.59 (1H, m), 7.0-7.03 (4H, m).

Workup

  1. concentrationconcentrated under reduced pressure
  2. customchromatographed with 1-2% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-f821570122c748f08f371e35f5041e16
Source dataset
uspto-grants-2014_01
Patent number
US08637546B2

Reaction notes

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