Diisopropylethylamine → N-[4-(2-Chloro-phenyl)-6-methyl-pyridin-3-yl]-3-methanesulfonyl-N-(2,2,2-trifluoro-ethyl)-5-trifluoromethyl-benzamide

HRID 878344Notes

Reaction equation

HRID 878344 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10][C:9]=1[NH:15][CH2:16][C:17]([F:20])([F:19])[F:18].FC1C=CC=C(OC)C=1C1C=CN=CC=1N(CC(F)(F)F)[C:37](=[O:52])[C:38]1[CH:43]=[C:42]([C:44]([F:47])([F:46])[F:45])[CH:41]=[C:40]([S:48]([CH3:51])(=[O:50])=[O:49])[CH:39]=1.CCN(C(C)C)C(C)C>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10][C:9]=1[N:15]([CH2:16][C:17]([F:20])([F:18])[F:19])[C:37](=[O:52])[C:38]1[CH:43]=[C:42]([C:44]([F:47])([F:45])[F:46])[CH:41]=[C:40]([S:48]([CH3:51])(=[O:50])=[O:49])[CH:39]=1

Participants

5

Reactant 3

HCID 81531Diisopropylethylamine2×HCID 706635194-(2-chlorophenyl)-6-methyl-N-(2,2,2-trifluoroethyl)pyridin-3-amineHCID 86670807N-[4-(2-Fluoro-6-methoxy-phenyl)-pyridin-3-yl]-3-methanesulfonyl-N-(2,2,2-trifluoro-ethyl)-5-trifluoromethyl-benzamide4×

Product 1

HCID 86670819N-[4-(2-Chloro-phenyl)-6-methyl-pyridin-3-yl]-3-methanesulfonyl-N-(2,2,2-trifluoro-ethyl)-5-trifluoromethyl-benzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(2-chlorophenyl)-6-methyl-N-(2,2,2-trifluoroethyl)pyridin-3-amine (0.066 g, 219 μmol) and 3-(methylsulfonyl)-5-(trifluoromethyl)benzoyl chloride (66.1 mg, 230 μmol, example 223, intermediate d) in CH2Cl2 (1 mL) was added DIPEA (56.7 mg, 76.7 μL, 439 μmol) and the clear yellow solution was stirred at room temperature for 4 hours. Another batch of 3-(methylsulfonyl)-5-(trifluoromethyl)benzoyl chloride (66.1 mg, 230 μmol, example 223, intermediate d) and DIPEA (56.7 mg, 76.7 μL, 439 μmol) were added and stirring was continued for another 48 hours. The compound was purified by silica gel chromatography on a 20 g column using an MPLC (ISCO) system eluting with EtOAc (isocratic). The product was further purified by preparative HPLC (Gemini NX column) using a gradient of MeOH:water (containing 0.1% formic acid) (20:80 to 98:2). Light brown solid (5%). MS (ESI): m/z=551.06 [M+H]+.

Workup

  1. stirringstirring
  2. waitwas continued for another 48 hours
  3. customThe compound was purified by silica gel chromatography on a 20 g column
  4. washeluting with EtOAc (isocratic)
  5. customThe product was further purified by preparative HPLC (Gemini NX column)

Sources & evidence

ORD record
ord-3c18d0d2988d424cbdeaa8d2ee65411f
Source dataset
uspto-grants-2015_03
Patent number
US08987307B2

Reaction notes

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