Boron trifluoride etherate → 5-Bromo-3-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine

HRID 2095610노트

반응식

HRID 2095610 반응식
[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([CH:11]([C:13]3[C:18]([Cl:19])=[CH:17][CH:16]=[C:15]([F:20])[C:14]=3[Cl:21])O)=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1.B(F)(F)F.[CH3:26]COCC.[Zn](C)C>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([CH:11]([C:13]3[C:18]([Cl:19])=[CH:17][CH:16]=[C:15]([F:20])[C:14]=3[Cl:21])[CH3:26])=[CH:9][NH:8][C:5]2=[N:6][CH:7]=1

참가 물질

5

반응물 3

HCID 8000Boron trifluoride etherateHCID 67004517(5-bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)(2,6-dichloro-3-fluorophenyl)methanolHCID 178477796HCID 178477796, 화합물

생성물 1

HCID 584314405-Bromo-3-[1-(2,6-dichloro-3-fluorophenyl)ethyl]-1H-pyrrolo[2,3-b]pyridine

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

(5-Bromo-1H-pyrrolo[2,3-b]pyridin-3-yl)-(2,6-dichloro-3-fluorophenyl)methanol (5.05 g, 12.9 mmol) was dissolved in anhydrous THF (100 mL). To this solution was added BF3.OEt2 (10.66 mL, 6.5 eq.) at −78° C. The resulting solution was stirred for 10 min at the same temp before a solution of ZnMe2 (35.60 mL, 5.5 eq., 2 N in toluene) was added. The resulting mixture was allowed to warm up to rt in 1 h. The solution was then stirred at 65° C. for 3.5 h. Reaction was monitored by LC-MS. After achieving >95% conversion, the reaction was allowed to cool down to rt. Then it was further cooled down to −78° C. and quenched by adding sat. aq. NH4Cl solution (10 mL). The mixture was slowly warmed up to rt. Solvents were removed under reduced pressure. To the residue was added aq. NaHCO3 solution and the mixture was then extracted with CHCl3 (100 mL×4). The organic extracts were combined, dried (Na2SO4), and concentrated in vacuo to give a crude residue which was purified by flash chromatography (eluent: 10% ethyl acetate in hexane). 1H NMR (400 MHz DMSO-d6): δ=11.85 (br. s., 1H), 8.21 (d, J=2.0 Hz, 1H), 7.49-7.59 (m, 2H), 7.41 (dd, J=8.8, 8.6 Hz, 1H), 7.30 (d, J=2.0 Hz, 1H), 5.11 (q, J=7.3 Hz, 1H), 1.80 (d, J=7.3 Hz, 3H); 13C NMR (100.6 MHz, DMSO-d6): δ=156.74 (JCF=247.4 Hz), 146.91, 142.24, 141.02, 129.37, 127.56, 125.98, 121.73 (JCF=19.8 Hz), 120.18, 115.98 (JCF=23.4 Hz), 113.62, 109.99, 33.53, 15.94. MS (ES+): m/z=386.93, 388.91, 390.89 [MH+]. HPLC: tR=4.17 min (ZQ3, polar—5 min).

후처리

  1. additionwas added
  2. customReaction
  3. temperatureto cool down to rt
  4. temperatureThen it was further cooled down to −78° C.
  5. customquenched
  6. additionby adding sat. aq. NH4Cl solution (10 mL)
  7. temperatureThe mixture was slowly warmed up to rt
  8. customSolvents were removed under reduced pressure
  9. additionTo the residue was added aq. NaHCO3 solution
  10. extractionthe mixture was then extracted with CHCl3 (100 mL×4)
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-5b5eb149059c467fa48699924f387fc1
출처 데이터셋
uspto-grants-2013_05
특허 번호
US08445510B2

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