Thionyl Chloride → (R)-N-(4-((3-(Dimethylamino)pyrrolidin-1-yl)methyl)-3-(trifluoromethyl)phenyl)-3-iodo-4-methylbenzamide
Reaction equation
[NH2:1][C:2]1[CH:16]=[CH:15][C:5]([CH2:6][N:7]2[CH2:11][CH2:10][C@@H:9]([N:12]([CH3:14])[CH3:13])[CH2:8]2)=[C:4]([C:17]([F:20])([F:19])[F:18])[CH:3]=1.[I:21][C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][C:30]=1[CH3:31])[C:25](Cl)=[O:26].IC1C=C(C=CC=1C)C(O)=O.O=S(Cl)Cl.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[CH3:13][N:12]([CH3:14])[C@@H:9]1[CH2:10][CH2:11][N:7]([CH2:6][C:5]2[CH:15]=[CH:16][C:2]([NH:1][C:25](=[O:26])[C:24]3[CH:28]=[CH:29][C:30]([CH3:31])=[C:22]([I:21])[CH:23]=3)=[CH:3][C:4]=2[C:17]([F:20])([F:18])[F:19])[CH2:8]1Participants
7
Reactant 5
Product 1
Reagents, catalysts & solvents 1
Procedure
To a cooled (0° C.) solution of (R)-1-(4-amino-2-(trifluoronnethyl)benzyl)-N,N-dimethylpyrrolidin-3-amine (3.79 mmol) in 14 mL DCM, under an atmosphere of N2, was added 3-Iodo-4-methylbenzoyl chloride (1.17 g, 4.17 mmol; CAS#52107-98-9, prepared from the reaction of 3-iodo-4-methylbenzoic acid and SOCl2) followed by dropwise addition of N,N-diisopropylethylamine (2.64 mL, 15.2 mmol). After stirring to ambient temperature over 1.5 h, the reaction mixture was concentrated and the crude product was purified by silica gel chromatography (eluted with 0-8% MeOH/DCM; MeOH was pre-saturated with ammonia gas), to provide 0.71 g of product as a thick yellow oil.
Workup
- concentrationthe reaction mixture was concentrated
- customthe crude product was purified by silica gel chromatography (eluted with 0-8% MeOH/DCM; MeOH was pre-saturated with ammonia gas)
Sources & evidence
- ORD record
- ord-e14fd7690916458a88ab9cea507649aa
- Source dataset
- uspto-grants-2015_05
- Patent number
- US09029533B2
Reaction notes
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