Triethylamine → 2-Chloro-N-(3-[(1E)-3-oxo-3-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}amino)prop-1-en-1-yl]phenyl)nicotinamide

HRID 2371062Notes

Reaction equation

HRID 2371062 reaction equation
[O:1]=[C:2]([NH:18][CH:19]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=1)[C:20]([F:23])([F:22])[F:21])/[CH:3]=[CH:4]/[C:5]1[CH:13]=[CH:12][C:8](C(O)=O)=[C:7](C(F)(F)F)[CH:6]=1.C([N:36](CC)CC)C.[Cl:41][C:42]1[N:50]=[CH:49][CH:48]=[CH:47][C:43]=1[C:44](Cl)=[O:45]>ClC(Cl)Cl.ClCCl>[Cl:41][C:42]1[N:50]=[CH:49][CH:48]=[CH:47][C:43]=1[C:44]([NH:36][C:7]1[CH:8]=[CH:12][CH:13]=[C:5](/[CH:4]=[CH:3]/[C:2](=[O:1])[NH:18][CH:19]([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=2)[C:20]([F:23])([F:22])[F:21])[CH:6]=1)=[O:45]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 27745412-Chloronicotinoyl chlorideHCID 866530664-[(1E)-3-Oxo-3-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}amino)prop-1-en-1-yl]-2-(trifluoromethyl)benzoic acid

Product 1

HCID 866893332-Chloro-N-(3-[(1E)-3-oxo-3-({2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]ethyl}amino)prop-1-en-1-yl]phenyl)nicotinamide

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolvent2×HCID 6344DichloromethaneSolvent

Procedure

100 mg (0.25 mmol) of (2E)-3-(3-aminophenyl)-N-{2,2,2-trifluoro-1-[3-(trifluoromethyl)phenyl]-ethyl}acrylamide from Example 3, Stage 2 and 33.8 mg (0.33 mmol) of triethylamine were initially charged in 1 ml of trichloromethane, and a solution of 49.8 mg (0.33 mmol) of 2-chloronicotinoyl chloride in 1 ml of trichloromethane was added. The reaction solution was stirred at room temperature for 18 hours, then diluted with dichloromethane, washed three times with water and dried over sodium sulphate. The solvent was distilled off under reduced pressure and the residue purified by preparative HPLC (solvent=water (A)+acetonitrile (B), gradient=40 min, from 10% B to 100% B, flow=18 ml/min).

Workup

  1. washwashed three times with water
  2. dry with materialdried over sodium sulphate
  3. distillationThe solvent was distilled off under reduced pressure
  4. customthe residue purified by preparative HPLC (solvent=water (A)+acetonitrile (B), gradient=40 min, from 10% B to 100% B, flow=18 ml/min)

Sources & evidence

ORD record
ord-2e4a0ed75e7d46709aaaefea9c7a269b
Source dataset
uspto-grants-2014_04
Patent number
US08710242B2

Reaction notes

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