Methyl(2,2,2-trifluoroethyl)amine hydrochloride → 2-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-6-(ethyl(2,2,2-trifluoroethyl)amino)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile

HRID 1968334Notes

Reaction equation

HRID 1968334 reaction equation
Cl.[CH2:2]([NH:4][CH2:5][C:6]([F:9])([F:8])[F:7])[CH3:3].Cl[C:11]1[C:16]([C:17]#[N:18])=[C:15]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][OH:28])=[CH:21][CH:20]=2)[C:14]([C:29]#[N:30])=[C:13]([S:31][CH2:32][C:33]2[N:34]=[C:35]([C:38]3[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][CH:39]=3)[S:36][CH:37]=2)[N:12]=1.Cl.FC(F)(F)CNC>CN(C=O)C.O.C1COCC1>[Cl:44][C:41]1[CH:40]=[CH:39][C:38]([C:35]2[S:36][CH:37]=[C:33]([CH2:32][S:31][C:13]3[C:14]([C:29]#[N:30])=[C:15]([C:19]4[CH:20]=[CH:21][C:22]([O:25][CH2:26][CH2:27][OH:28])=[CH:23][CH:24]=4)[C:16]([C:17]#[N:18])=[C:11]([N:4]([CH2:2][CH3:3])[CH2:5][C:6]([F:9])([F:8])[F:7])[N:12]=3)[N:34]=2)=[CH:43][CH:42]=1

Participants

6

Reactant 3

HCID 22496068Methyl(2,2,2-trifluoroethyl)amine hydrochlorideHCID 42919629N-ethyl-N-(trifluoroethyl)amine hydrochlorideHCID 866438472-Chloro-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile

Product 1

HCID 687635692-({(2-(4-Chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-6-(ethyl(2,2,2-trifluoroethyl)amino)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 21881883Oxolane--water (1/1)Solvent

Procedure

133 mg (0.81 mmol) of N-ethyl-2,2,2-trifluoroethanamine hydrochloride were dissolved in 2 ml of DMF, 130 mg Amberlyst A-21 were added and the mixture was stirred at RT for 30 min. The mixture was filtered off and added to 100 mg (0.14 mmol, purity about 74%) of 2-chloro-6-({(2-(4-chlorophenyl)-1,3-thiazol-4-yl)methyl}sulfanyl)-4-(4-(2-hydroxyethoxy)phenyl)pyridine-3,5-dicarbonitrile (Example 2A), and the solution was stirred at RT overnight. The mixture was then warmed to 60° C. and stirred at this temperature overnight. In a separate flask, another 87 mg (0.54 mmol) of 2,2,2-trifluoro-N-methylethanamine hydrochloride were then dissolved in 0.5 ml of DMF, 88 mg of Amberlyst A-21 were added and the mixture was stirred at RT for 30 min. The mixture was filtered off and added to the first solution. The reaction mixture obtained was stirred at 100° C. for 4.5 h. The mixture was then diluted with a little water/THF and purified by preparative HPLC (acetonitrile/water+0.1% TFA). This gave 37 mg (41% of theory) of the target compound.

Workup

  1. addition130 mg Amberlyst A-21 were added
  2. filtrationThe mixture was filtered off
  3. stirringthe solution was stirred at RT overnight
  4. temperatureThe mixture was then warmed to 60° C.
  5. stirringstirred at this temperature overnight
  6. addition88 mg of Amberlyst A-21 were added
  7. stirringthe mixture was stirred at RT for 30 min
  8. filtrationThe mixture was filtered off
  9. additionadded to the first solution
  10. customThe reaction mixture obtained
  11. stirringwas stirred at 100° C. for 4.5 h
  12. custompurified by preparative HPLC (acetonitrile/water+0.1% TFA)

Sources & evidence

ORD record
ord-1f6bf33e7c3f4fa691873844811a37eb
Source dataset
uspto-grants-2013_04
Patent number
US08420825B2

Reaction notes

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