Methyl(2,2,2-trifluoroethyl)amine hydrochloride → HCID 68764724, compound

HRID 1621335Notes

Reaction equation

HRID 1621335 reaction equation
Cl.[F:2][C:3]([F:8])([F:7])[CH2:4][NH:5][CH3:6].Cl[C:10]1[C:15]([C:16]#[N:17])=[C:14]([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][OH:27])=[CH:20][CH:19]=2)[C:13]([C:28]#[N:29])=[C:12]([S:30][CH2:31][C:32]2[N:33]=[C:34]([C:37]3[CH:42]=[CH:41][C:40]([Cl:43])=[CH:39][CH:38]=3)[S:35][CH:36]=2)[N:11]=1>CN(C=O)C.O.C1COCC1>[Cl:43][C:40]1[CH:39]=[CH:38][C:37]([C:34]2[S:35][CH:36]=[C:32]([CH2:31][S:30][C:12]3[C:13]([C:28]#[N:29])=[C:14]([C:18]4[CH:19]=[CH:20][C:21]([O:24][CH2:25][CH2:26][OH:27])=[CH:22][CH:23]=4)[C:15]([C:16]#[N:17])=[C:10]([N:5]([CH3:6])[CH2:4][C:3]([F:8])([F:7])[F:2])[N:11]=3)[N:33]=2)=[CH:42][CH:41]=1

Participants

5

Reactant 2

HCID 22496068Methyl(2,2,2-trifluoroethyl)amine hydrochloride2×HCID 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 68764724HCID 68764724, compound

Reagents, catalysts & solvents 2

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

Procedure

41 mg (0.27 mmol) of 2,2,2-trifluoro-N-methylethanamine hydrochloride were dissolved in 2 ml of DMF, 40 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 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. In a separate flask, another 82 mg (0.54 mmol) of 2,2,2-trifluoro-N-methylethanamine hydrochloride were then dissolved in 0.5 ml of DMF, 80 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 RT overnight. The mixture was then warmed to 60° C., and the reaction mixture was stirred at this temperature overnight, after which it was heated to 100° C. After stirring at 100° C. overnight, the mixture was diluted with a little water/THF and purified by preparative HPLC (acetonitrile/water+0.1% TFA). This gave 64 mg (74% of theory) of the target compound.

Workup

  1. addition40 mg of Amberlyst A-21 were added
  2. filtrationThe mixture was filtered off
  3. stirringthe solution was stirred at RT overnight
  4. addition80 mg of Amberlyst A-21 were added
  5. stirringthe mixture was stirred at RT for 30 min
  6. filtrationThe mixture was filtered off
  7. additionadded to the first solution
  8. customThe reaction mixture obtained
  9. stirringwas stirred at RT overnight
  10. temperatureThe mixture was then warmed to 60° C.
  11. stirringthe reaction mixture was stirred at this temperature overnight
  12. temperatureafter which it was heated to 100° C
  13. stirringAfter stirring at 100° C. overnight
  14. custompurified by preparative HPLC (acetonitrile/water+0.1% TFA)

Sources & evidence

ORD record
ord-1f9f668fc34a47059d34d56fa7942b53
Source dataset
uspto-grants-2014_07
Patent number
US08772498B2

Reaction notes

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