Pyridine → Ethyl 1-(6-{2-[(4-methoxyphenyl)ethynyl]phenyl}pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

HRID 1255208ノート

反応式

HRID 1255208 の反応式
O[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:13]=[C:12]([N:14]2[C:18]([C:19]([F:22])([F:21])[F:20])=[C:17]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:16]=[N:15]2)[CH:11]=[CH:10][CH:9]=1.N1C=CC=CC=1.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[O-]S(C(F)(F)F)(=O)=O.[CH3:57][O:58][C:59]1[CH:64]=[CH:63][C:62]([C:65]#[CH:66])=[CH:61][CH:60]=1.C(N(CC)CC)C>C(Cl)Cl.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cu]I>[CH3:57][O:58][C:59]1[CH:64]=[CH:63][C:62]([C:65]#[C:66][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=2[C:8]2[N:13]=[C:12]([N:14]3[C:18]([C:19]([F:20])([F:21])[F:22])=[C:17]([C:23]([O:25][CH2:26][CH3:27])=[O:24])[CH:16]=[N:15]3)[CH:11]=[CH:10][CH:9]=2)=[CH:61][CH:60]=1

参加物

10

反応物 6

HCID 1049PyridineHCID 8471TriethylamineHCID 67749Trifluoromethanesulfonic anhydrideHCID 2510201-Ethynyl-4-methoxybenzeneHCID 2758875TrifluoromethanesulfonateHCID 136298134Ethyl 1-[6-(2-hydroxylphenyl)pyridine-2-yl]-5-trifluoromethyl-1H-pyrazole-4-carboxylate

生成物 1

HCID 67158916Ethyl 1-(6-{2-[(4-methoxyphenyl)ethynyl]phenyl}pyridin-2-yl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 67553Tetrabutylammonium Iodide触媒HCID 6344Dichloromethane溶媒

実験手順

To a cooled (0° C.) solution of the title compound from Example 1 Step B (374 mg, 0.991 mmol) and pyridine (0.241 mL, 2.97 mmol) in DCM (5 mL) was added trifluoromethanesulfonic anhydride (0.251 mL, 1.487 mmol). The cooling bath was immediately removed, and the reaction mixture was allowed to stir at ambient temperature. After 45 min, the reaction mixture was poured into water and extracted with DCM. The layers were separated and the organic phase was concentrated in vacuo, yielding material that was sufficiently pure for use in the next step: LCMS m/z 510.0 [M+H]+. To a flask containing the unpurified triflate were added copper (I) iodide (56.1 mg, 0.294 mmol), trans-dichlorobis(triphenylphosphine) palladium (II) (68.9 mg, 0.098 mmol), tetrabutylammonium iodide (1.088 g, 2.94 mmol), and 4-methoxyphenylacetylene (195 mg, 1.47 mmol). The flask with flushed with nitrogen, and acetonitrile (5 mL) was added. The mixture was degassed with nitrogen, triethylamine (1.00 mL, 7.17 mmol) was added, and the resulting mixture was stirred at ambient temperature. After 20 h, the reaction mixture was concentrated in vacuo. Purification by flash chromatography on silica gel (0 to 30% EtOAc in hexanes, then 30 to 100% EtOAc in hexanes) provided the title compound: LCMS m/z 492.1 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 8.32 (d, J=8.0 Hz, 1H), 8.14 (s, 1H), 7.99 (t, J=8.0 Hz, 1H), 7.89 (d, J=7.5 Hz, 1H), 7.65-7.63 (m, 2H), 7.47-7.39 (m, 2H), 7.33 (d, J=8.5 Hz, 2H), 6.86 (d, J=8.5 Hz, 2H), 4.38 (q, J=7.0 Hz, 2H), 3.82 (s, 3H), 1.39 (t, J=7.0 Hz, 3H).

後処理

  1. customThe cooling bath was immediately removed
  2. additionthe reaction mixture was poured into water
  3. extractionextracted with DCM
  4. customThe layers were separated
  5. concentrationthe organic phase was concentrated in vacuo
  6. customyielding material that
  7. customThe flask with flushed with nitrogen, and acetonitrile (5 mL)
  8. additionwas added
  9. additionwas added
  10. stirringthe resulting mixture was stirred at ambient temperature
  11. waitAfter 20 h
  12. concentrationthe reaction mixture was concentrated in vacuo
  13. customPurification by flash chromatography on silica gel (0 to 30% EtOAc in hexanes

出典と根拠

ORDレコード
ord-580649e565ba4524a121488007d71c62
出典データセット
uspto-grants-2013_06
特許番号
US08455638B2

反応ノート

読み込み中…