3,5-Bis(trifluoromethyl)benzoic acid → N-[4-(4-Fluoro-2-methoxy-phenyl)-pyridin-3-yl]-N-(2-methanesulfonyl-ethyl)-3,5-bis-tri fluoro methyl-benzamide

HRID 878212Notes

Reaction equation

HRID 878212 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH2:31][CH2:32][S:33]([CH3:36])(=[O:35])=[O:34])[C:15](=[O:30])[C:16]2[CH:21]=[C:20]([C:22]([F:25])([F:24])[F:23])N=[C:18]([C:26]([F:29])([F:28])[F:27])[CH:17]=2)=[C:4]([O:37][CH3:38])[CH:3]=1.F[C:40](F)(F)C1C=C(C=C(C(F)(F)F)C=1)C(O)=O>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[CH:10][C:9]=2[N:14]([CH2:31][CH2:32][S:33]([CH3:36])(=[O:34])=[O:35])[C:15](=[O:30])[C:16]2[CH:17]=[C:18]([C:26]([F:28])([F:27])[F:29])[CH:40]=[C:20]([C:22]([F:24])([F:23])[F:25])[CH:21]=2)=[C:4]([O:37][CH3:38])[CH:3]=1

Participants

3

Reactant 2

HCID 128893,5-Bis(trifluoromethyl)benzoic acidHCID 86670775N-[4-(4-Fluoro-2-methoxy-phenyl)-pyridin-3-yl]-N-(2-methanesulfonyl-ethyl)-2,6-bis-trifluoromethyl-isonicotinamide

Product 1

HCID 86670789N-[4-(4-Fluoro-2-methoxy-phenyl)-pyridin-3-yl]-N-(2-methanesulfonyl-ethyl)-3,5-bis-tri fluoro methyl-benzamide

Procedure

The title compound was prepared in analogy to example 90, from [4-(4-fluoro-2-methoxy-phenyl)-pyridin-3-yl]-(2-methanesulfonyl-ethyl)-amine (example 162, intermediate) and 3,5-bis(trifluoromethyl)benzoic acid (CAS RN 725-89-3) after a reaction time of 40 hours. The compound was purified by silica gel chromatography using a MPLC system (ISCO) and a 10 g and 5 g column, respectively, eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). A third chromatography, using preparative HPLC (Gemini NX column) eluting with a gradient of methanol:water (containing 0.05% formic acid) (20:80 to 98:2), yielded the product as a colorless solid (4%). MS (ESI): m/z=565.10 [M+H]+.

Workup

  1. customThe compound was purified by silica gel chromatography
  2. washa 10 g and 5 g column, respectively, eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100)
  3. washeluting with a gradient of methanol

Sources & evidence

ORD record
ord-da45fe56e9014806bffc7af062d57446
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

Loading…