Hydrochloric Acid → 7-bromo-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

HRID 37784

반응식

HRID 37784 반응식
Cl.[Br:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[NH:9]N.[N:11]12[CH2:19][CH2:18][CH:15]([CH2:16][CH2:17]1)[C:14](=O)[CH2:13][CH2:12]2.Cl>C(O)(=O)C>[Br:2][C:3]1[C:4]2[NH:9][C:14]3[CH:15]4[CH2:18][CH2:19][N:11]([CH2:12][C:13]=3[C:5]=2[CH:6]=[CH:7][CH:8]=1)[CH2:17][CH2:16]4

참가 물질

5

반응물 3

HCID 313Hydrochloric AcidHCID 27239122-Bromophenylhydrazine hydrochlorideHCID 64203071-Azabicyclo[3.2.2]nonan-4-one

생성물 1

HCID 672401637-bromo-3,4,5,6-tetrahydro-1H-2,5-ethanoazepino[4,3-b]indole

시약·촉매·용매 1

HCID 176Acetic Acid용매

반응 조건

온도
105 °C

실험 절차

A mixture of (2-bromophenyl)hydrazine hydrochloride (1.5 g, 6.71 mmol; Aldrich) and the product of Example 1A (0.94 g, 6.71 mmol) was combined with a solution of HCl in acetic acid (1.0 M, 20 mL; Aldrich) and stirred at 105° C. for 18 hours. The reaction mixture was concentrated under vacuum. The residue was taken up in toluene (100 mL) and concentrated under vacuum to remove most of the acetic acid (the azeotrope procedure was repeated a second time). The residue was dissolved in dimethyl sulfoxide (20 mL) and purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 50×100 mm, flow rate 100 mL/minute, 40-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound: 1H NMR (400 MHz, methanol-d4 ) δ ppm 2.05-2.13 (m, 4 H), 3.08 (pent, J=6.9 Hz, 2 H), 3.15 (pent, J=3.6 Hz, 1 H), 3.26 (pent, J=7.2 Hz, 2 H), 4.23 (s, 2 H), 6.88 (t, J=7.8 Hz, 1 H), 7.19 (d, J=7.6 Hz, 1 H), 7.27 (d, J=7.9 Hz, 1 H); MS (APCI) m/z 291/293 (M+H)+.

후처리

  1. concentrationThe reaction mixture was concentrated under vacuum
  2. concentrationconcentrated under vacuum
  3. customto remove most of the acetic acid (the azeotrope procedure
  4. dissolutionThe residue was dissolved in dimethyl sulfoxide (20 mL)
  5. custompurified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 50×100 mm, flow rate 100 mL/minute, 40-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

출처 및 근거

ORD 기록
ord-5ebcb7ea6978407eb34d8435382f8dee
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524703B2

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