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Diisopropylethylamine → N-(3,5-Bis-trifluoromethyl-benzyl)-6-chloro-4-(2-chloro-phenyl)-N-methyl-nicotinamide

HRID 1835340
Notes
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Reaction equation

HRID 1835340 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])[C:5]([C:6]([OH:8])=O)=[CH:4][N:3]=1.[F:18][C:19]([F:34])([F:33])[C:20]1[CH:21]=[C:22]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[CH2:23][NH:24][CH3:25].C(N(C(C)C)C(C)C)C>CN(C)C=O.CN(C1C=CN=CC=1)C.ClCCl>[F:18][C:19]([F:33])([F:34])[C:20]1[CH:21]=[C:22]([CH:26]=[C:27]([C:29]([F:32])([F:31])[F:30])[CH:28]=1)[CH2:23][N:24]([CH3:25])[C:6](=[O:8])[C:5]1[C:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[Cl:17])=[CH:10][C:2]([Cl:1])=[N:3][CH:4]=1
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 10956204{[3,5-Bis(trifluoromethyl)phenyl]methyl}(methyl)amineHCID 235028066-Chloro-4-(2-chloro-phenyl)-nicotinic acid

Product 1

HCID 23502843N-(3,5-Bis-trifluoromethyl-benzyl)-6-chloro-4-(2-chloro-phenyl)-N-methyl-nicotinamideYield 84%

Reagents, catalysts & solvents 3

HCID 6228
Dimethylformamide
Catalyst
HCID 142844-(Dimethylamino)pyridineCatalyst
HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of 300 mg (1.12 mmol) 6-chloro-4-(2-chloro-phenyl)-nicotinic acid (Example 24, step e)) in 12 ml dichloromethane 0.15 ml (1.7 mmol) oxalyl chloride and one drop of N,N-dimethylformamide were added at 0° C. After completed addition the reaction mixture was allowed to warm to room temperature and stirred for 1 h. The reaction mixture was concentrated in vactio. The residue was redissolved in 6 ml dichloromethane and added dropwise to a solution of 432 mg (1.68 mmol) (3,5-bis-trifluoromethyl-benzyl)-methyl-amine, 0.39 ml (2.2 mmol) N-ethyldiisopropylamine and 7 mg (0.06 mmol) 4-(N,N-dimethylamino)pyridine in 6 ml dichloromethane at 0° C. After completed addition the reaction mixture was allowed to warm to room temperature and stirred over night. The reaction mixture was diluted with dichloromethane and washed with two portions of 1 M aqueous hydrochloric acid solution. The combined aqueous layers were extracted with dichloromethane. The combined organic extracts were washed with two portions of 1 M aqueous sodium hydroxide solution. The combined basic aqueous layers were extracted with dichloromethane. The combined organic extracts were dried with sodium sulfate and concentrated. Column chromatography afforded 475 mg (84%) of the title compound as a light yellow amorphous mass.

Workup

  1. additionaddition the reaction mixture
  2. concentrationThe reaction mixture was concentrated in vactio
  3. dissolutionThe residue was redissolved in 6 ml dichloromethane
  4. additionaddition the reaction mixture
  5. temperatureto warm to room temperature
  6. stirringstirred over night
  7. washwashed with two portions of 1 M aqueous hydrochloric acid solution
  8. extractionThe combined aqueous layers were extracted with dichloromethane
  9. washThe combined organic extracts were washed with two portions of 1 M aqueous sodium hydroxide solution
  10. extractionThe combined basic aqueous layers were extracted with dichloromethane
  11. dry with materialThe combined organic extracts were dried with sodium sulfate
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-b6d3dda420d847e29203f0592b33feec
Source dataset
uspto-grants-2004_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06770637B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes