Oxalyl chloride → (E)-4,4-Difluoro-N-[(3S)-1-(5-methyl-3-pyridyl)pyrrolidin-3-yl]pent-2-enamide
Reaction equation
[F:1][C:2]([F:9])([CH3:8])/[CH:3]=[CH:4]/[C:5]([OH:7])=O.C(Cl)(=O)C(Cl)=O.Cl.Cl.Cl.[CH3:19][C:20]1[CH:25]=CN=[C:22]([N:26]2[CH2:30][CH2:29][C@H:28]([NH2:31])[CH2:27]2)[CH:21]=1.[CH2:32]([N:34](C(C)C)C(C)C)C>ClCCl.CN(C=O)C>[F:9][C:2]([F:1])([CH3:8])/[CH:3]=[CH:4]/[C:5]([NH:31][C@H:28]1[CH2:29][CH2:30][N:26]([C:22]2[CH:32]=[N:34][CH:25]=[C:20]([CH3:19])[CH:21]=2)[CH2:27]1)=[O:7]Participants
7
Reactant 4
Product 1
Reagents, catalysts & solvents 2
Procedure
(E)-4,4-Difluoropent-2-enoic acid (22 mg, 0.16 mmol) was dissolved in dichloromethane (1 ml), oxalyl chloride (14 μl, 0.16 mol) and one drop of DMF were added and the resulting solution was stirred at room temperature for 15 minutes. This solution was added to a solution of (3S)-1-(4-methyl-2-pyridyl)pyrrolidin-3-amine trihydrochloride (29 mg, 0.1 mmol) in DCM (2 ml). Ethyl-N,N-diisopropylamine (DIPEA, 70 μl, 0.4 mmol) was added and the resulting mixture was stirred at room temperature overnight. The mixture was concentrated under reduced pressure and the resulting residue was purified by preparative HPLC (Waters XBridge, gradient of water containing 0.1% NH3 and acetonitrile) to yield 20 mg of a solid (0.067 mmol, 67%).
Workup
- stirringthe resulting mixture was stirred at room temperature overnight
- concentrationThe mixture was concentrated under reduced pressure
- customthe resulting residue was purified by preparative HPLC (Waters XBridge, gradient of water containing 0.1% NH3 and acetonitrile)
Sources & evidence
- ORD record
- ord-786d5b9bc954410bbbb9899b4d1be446
- Source dataset
- uspto-grants-2016_02
- Patent number
- US09260441B2
Reaction notes
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