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

HRID 37784

反応式

HRID 37784 の反応式
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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 176Acetic Acid溶媒

反応条件

温度
105 °C

実験手順

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)+.

後処理

  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)]

出典と根拠

ORDレコード
ord-5ebcb7ea6978407eb34d8435382f8dee
出典データセット
uspto-grants-2013_09
特許番号
US08524703B2

関連ノート

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