1,2-Dichloroethane → 4-(4-chloro-2-fluorophenyl)-N-isopropylnicotinamide
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=C[C:25]2N(O)N=[N:28][C:26]=2[CH:27]=1.CCN(C(C)C)C(C)C.CC(N)C>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([C:14]([NH:28][CH:26]([CH3:27])[CH3:25])=[O:16])=[CH:12][N:11]=[CH:10][CH:9]=2)=[C:4]([F:17])[CH:3]=1Participants
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of 4-(4-chloro-2-fluorophenyl)nicotinic acid (400 mg, 1.590 mmol) (prepared as in Ex. 2, Part A) in DMF (6 mL) cooled to 0° C. was added EDC (457 mg, 2.384 mmol) and HOBT (487 mg, 3.18 mmol) and the mixture was stirred for 5 min. To the resultant solution DIPEA (0.83 mL, 4.77 mmol) followed by propan-2-amine (470 mg, 7.95 mmol) were added 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 4-(4-chloro-2-fluorophenyl)-N-isopropylnicotinamide (480 mg, 1.64 mmol, 100%) as an off-white solid. LC/MS (ESI) m/e 293.2 [(M+H)+, calcd for C15H15ClFN2O 293.1]; LC/MS retention time (method C): tR=1.84 min.
Workup
- additionwere added
- 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-d5d1af31ef5f43279a09dacc66a18b31
- Source dataset
- uspto-grants-2014_12
- Patent number
- US08901305B2
Reaction notes
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