p-Toluenesulfonic acid → 4,6-dichloro-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine

HRID 81262

반응식

HRID 81262 반응식
[Cl:1][C:2]1[C:7]2[NH:8][CH:9]=[N:10][C:6]=2[CH:5]=[C:4]([Cl:11])[N:3]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[F:31][C:32]([F:42])([F:41])[C:33]1[CH:40]=[CH:39][C:36]([CH2:37]O)=[CH:35][CH:34]=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1.CCOC(C)=O>[Cl:1][C:2]1[C:7]2[N:8]([CH2:37][C:36]3[CH:35]=[CH:34][C:33]([C:32]([F:31])([F:41])[F:42])=[CH:40][CH:39]=3)[CH:9]=[N:10][C:6]=2[CH:5]=[C:4]([Cl:11])[N:3]=1

참가 물질

8

반응물 5

HCID 6101p-Toluenesulfonic acidHCID 11776TriphenylphosphineHCID 676844-(Trifluoromethyl)benzenemethanolHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 178477826HCID 178477826, 화합물

생성물 1

HCID 867244584,6-dichloro-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine

시약·촉매·용매 2

HCID 8028Tetrahydrofuran용매2회HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

4,6-dichloro-3H-imidazo[4,5-c]pyridine (500 mg, 2.6 mmol), PPh3 (762 mg, 2.91 mmol) and THF (20 mL) were combined and stirred under a nitrogen atmosphere. A solution of 4-trifluoromethyl benzyl alcohol (513 mg, 2.91 mmol) in THF (5 mL) was added at rt. The reaction mixture was cooled to 0° C., and diisopropyl azodicarboxylate (587 mg, 2.91 mmol) was added dropwise. The reaction was warmed to rt and stirred overnight under N2. The reaction was then diluted with EtOAc, washed with brine, dried over Na2SO4, filtered, and concentrated. The crude residue was dissolved in EtOAc (20 ml), p-toluenesulfonic acid (500 mg, 2.91 mmol) was added at rt, and the mixture was stirred for 3 h. The precipitate which formed was collected by filtration and rinsed with EtOAc. The collected precipitate was slurried in EtOAc (50 mL) and was stirred vigorously with aqueous sat'd NaHCO3 (5 mL) for 30 min. The organic layer was separated, and the aqueous layer was extracted several times with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated. The crude product was purified by silica gel chromatography with 20% to 100% EtOAc/hexanes to obtain the desired isomer, 4,6-dichloro-3-(4-(trifluoromethyl)benzyl)-3H-imidazo[4,5-c]pyridine. 1H NMR (400 MHz, CDCl3): δ8.85 (s, 1H); 7.96 (s, 1H); 7.71 (d, J=8.0 Hz, 2H), 7.33 (d, J=8.0 Hz, 2H), 5.89 (s, 2H). MS APCl calc'd. for C14H8Cl2F3N3 [M+H]+ 346, found 346.

후처리

  1. temperatureThe reaction was warmed to rt
  2. stirringstirred overnight under N2
  3. washwashed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe crude residue was dissolved in EtOAc (20 ml)
  8. stirringthe mixture was stirred for 3 h
  9. customThe precipitate which formed
  10. filtrationwas collected by filtration
  11. washrinsed with EtOAc
  12. stirringwas stirred vigorously with aqueous sat'd NaHCO3 (5 mL) for 30 min
  13. customThe organic layer was separated
  14. extractionthe aqueous layer was extracted several times with EtOAc
  15. dry with materialThe combined organic layers were dried over Na2SO4
  16. filtrationfiltered
  17. concentrationconcentrated
  18. customThe crude product was purified by silica gel chromatography with 20% to 100% EtOAc/hexanes

출처 및 근거

ORD 기록
ord-b1315f3f871a496ba5c084e682d442ba
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846657B2

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