Hydrochloric Acid → 8-Bromo-6-methyl-3,4,5,6-tetrahydro-1H-2,5-methanoazepino[4,3-b]indole

HRID 1521463노트

반응식

HRID 1521463 반응식
[Br:1][C:2]1[CH:3]=[C:4]([N:8]([CH3:10])N)[CH:5]=[CH:6][CH:7]=1.[N:11]12[CH2:18][CH:15]([CH2:16][CH2:17]1)[C:14](=O)[CH2:13][CH2:12]2.Cl>C(O)(C)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[C:13]3[CH2:12][N:11]4[CH2:18][CH:15]([CH2:16][CH2:17]4)[C:14]=3[N:8]([CH3:10])[C:4]=2[CH:3]=1

참가 물질

5

반응물 3

HCID 313Hydrochloric AcidHCID 100804071-Azabicyclo(3.2.1)octan-4-oneHCID 534011811-(3-Bromophenyl)-1-methylhydrazine

생성물 1

HCID 580794278-Bromo-6-methyl-3,4,5,6-tetrahydro-1H-2,5-methanoazepino[4,3-b]indole수율 95%

시약·촉매·용매 1

HCID 3776Isopropanol용매

실험 절차

1-(3-Bromophenyl)-1-methylhydrazine (0.48 g, 2.3 mmol) and 1-azabicyclo[3.2.1]octan-4-one (0.33 g, 2.6 mmol) were dissolved in isopropanol (3 mL), and concentrated aqueous HCl (0.75 mL) was added. The reaction mixture was heated to reflux for 18 h, concentrated and basified using 2 N NaOH. The aqueous layer was extracted with methylene chloride (3×). The combined organic extracts were dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by flash column chromatography (silica gel, 10%-100% solvent mixture B in ethyl acetate; solvent mixture B=80:18:2 ethyl acetate/methanol/concentrated ammonium hydroxide) to give the title compound (634 mg, 95%) as a yellow semisolid: 1H NMR (300 MHz, CDCl3) δ 7.42 (d, J=2.5 Hz, 1H), 7.20 (d, J=13.5 Hz, 1H), 7.14 (d, J=13.5 Hz, 1H), 4.40 (d, J=26.5 Hz, 1H), 3.72 (d, J=26.0 Hz, 1H), 3.63 (s, 3H), 3.34-3.25 (m, 1H), 3.20-3.17 (m, 2H), 3.17-3.13 (m, 1H), 2.97-2.92 (m, 1H), 2.87-2.76 (m, 2H).

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 18 h
  3. concentrationconcentrated
  4. extractionThe aqueous layer was extracted with methylene chloride (3×)
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe residue was purified by flash column chromatography (silica gel, 10%-100% solvent mixture B in ethyl acetate; solvent mixture B=80:18:2 ethyl acetate/methanol/concentrated ammonium hydroxide)

출처 및 근거

ORD 기록
ord-ca35c3b7e43843b58c7f9ebf68280228
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09073925B2

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