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

HRID 1255208노트

반응식

HRID 1255208 반응식
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

참가 물질

10

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 67553Tetrabutylammonium Iodide촉매HCID 6344Dichloromethane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-580649e565ba4524a121488007d71c62
출처 데이터셋
uspto-grants-2013_06
특허 번호
US08455638B2

반응 노트

불러오는 중…