1,2-Dichloroethane → N-benzyl-4-(4-chloro-2-fluorophenyl)nicotinamide
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]([OH:16])=O)=[CH:12][N:11]=[CH:10][CH:9]=2)=[C:4]([F:17])[CH:3]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[CH2:41]([NH2:48])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1>CN(C=O)C>[CH2:41]([NH:48][C:14](=[O:16])[C:13]1[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][C:4]=2[F:17])=[CH:9][CH:10]=[N:11][CH:12]=1)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 4-(4-chloro-2-fluorophenyl)nicotinic acid (600 mg, 2.38 mmol) (as prepared in Ex. 2, Part A) in DMF (6 mL) cooled to 0° C. was added EDC (457 mg, 2.38 mmol) and HOBT (365 mg, 2.38 mmol) and the mixture was stirred for 5 min. To the resultant solution was added DIPEA (0.416 mL, 2.384 mmol) followed by benzyl amine (307 mg, 2.86 mmol) and the mixture was stirred at room temperature for 12 h. The reaction mixture was treated with ice and extracted with ethyl acetate (3×10 mL). The combined organic layers were washed with brine (1×10 mL), dried (Na2SO4) and concentrated under reduced pressure to afford N-benzyl-4-(4-chloro-2-fluorophenyl)nicotinamide (680 mg, 2.00 mmol, 84% yield). LC/MS (ESI) m/e 341.0 [(M+H)+, calcd for C19H15ClFN2O 341.1]; LC/MS retention time (method A): tR=1.73 min.
Workup
- stirringthe mixture was stirred at room temperature for 12 h
- additionThe reaction mixture was treated with ice
- extractionextracted with ethyl acetate (3×10 mL)
- washThe combined organic layers were washed with brine (1×10 mL)
- dry with materialdried (Na2SO4)
- concentrationconcentrated under reduced pressure
Sources & evidence
- ORD record
- ord-7f394ee3ccd2499cb50a580f650ba006
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08901305B2
Reaction notes
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