Chloroform → trans-N-[3-hydroxy-1-[2-(2-pyrimidinylamino)ethyl]-4-piperidinyl]-3-(trifluoromethyl)benzamide

HRID 654190Notes

Reaction equation

HRID 654190 reaction equation
[NH2:1][C@@H:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][NH:10][C:11]2[N:16]=[CH:15][CH:14]=[CH:13][N:12]=2)[CH2:4][C@H:3]1[OH:17].ClC(Cl)Cl.[F:22][C:23]([F:34])([F:33])[C:24]1[CH:25]=[C:26]([CH:30]=[CH:31][CH:32]=1)[C:27](Cl)=[O:28]>C(N(CC)CC)C>[OH:17][C@H:3]1[C@H:2]([NH:1][C:27](=[O:28])[C:26]2[CH:30]=[CH:31][CH:32]=[C:24]([C:23]([F:22])([F:33])[F:34])[CH:25]=2)[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][NH:10][C:11]2[N:12]=[CH:13][CH:14]=[CH:15][N:16]=2)[CH2:4]1

Participants

5

Reactant 3

HCID 6212ChloroformHCID 752573-(Trifluoromethyl)benzoyl chlorideHCID 67833360trans-4-Amino-1-[2-(2-pyrimidinylamino)ethyl]-3-piperidinol

Product 1

HCID 14854949trans-N-[3-hydroxy-1-[2-(2-pyrimidinylamino)ethyl]-4-piperidinyl]-3-(trifluoromethyl)benzamideYield 50.5%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

To a stirred solution of 2.37 parts of trans-4-amino-1-[2-(2-pyrimidinylamino)ethyl]-3-piperidinol in 120 parts of trichloromethane were added 2.08 parts of 3-(trifluoromethyl)benzoyl chloride. The whole was stirred for 15 minutes in an ice bath. After the addition of 1.26 parts of N,N-diethylethanamine, stirring was continued for 18 hours and the temperature was allowed to reach room temperature. The reaction mixture was washed with a sodium carbonate solution and water, dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol, saturated with ammonia, (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated. The residue was suspended in 2,2'-oxybispropane. The product was filtered off and dried, yielding 2.07 parts (50.5%) of trans-N-[3-hydroxy-1-[2-(2-pyrimidinylamino)ethyl]-4-piperidinyl]-3-(trifluoromethyl)benzamide; mp. 148.3° C. (compound 65).

Workup

  1. stirringstirring
  2. waitwas continued for 18 hours
  3. customto reach room temperature
  4. washThe reaction mixture was washed with a sodium carbonate solution and water
  5. customdried
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by column chromatography over silica gel using
  9. additiona mixture of trichloromethane and methanol
  10. customThe pure fractions were collected
  11. customthe eluent was evaporated
  12. filtrationThe product was filtered off
  13. customdried

Sources & evidence

ORD record
ord-7d497965bdc44fdaa1d9099303b33939
Source dataset
uspto-grants-1992_07
Patent number
US05130312

Reaction notes

Loading…