2-(Benzyloxy)-4-hydrazinylbenzonitrile → methyl 2-(3-(benzyloxy)-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate

HRID 505725ノート

反応式

HRID 505725 の反応式
[CH2:1]([O:8][C:9]1[CH:16]=[C:15]([NH:17][NH2:18])[CH:14]=[CH:13][C:10]=1[C:11]#[N:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:19]1([CH:24]=[C:25]2[CH2:34][CH2:33][C:32]3[CH:31]=[C:30]([C:35]([O:37][CH3:38])=[O:36])[CH:29]=[CH:28][C:27]=3[C:26]2=O)[CH2:23][CH2:22][CH2:21][CH2:20]1>Cl.C(O)C>[CH2:1]([O:8][C:9]1[CH:16]=[C:15]([N:17]2[CH:24]([CH:19]3[CH2:20][CH2:21][CH2:22][CH2:23]3)[CH:25]3[C:26]([C:27]4[CH:28]=[CH:29][C:30]([C:35]([O:37][CH3:38])=[O:36])=[CH:31][C:32]=4[CH2:33][CH2:34]3)=[N:18]2)[CH:14]=[CH:13][C:10]=1[C:11]#[N:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

5

反応物 2

HCID 469151942-(Benzyloxy)-4-hydrazinylbenzonitrileHCID 66722547Methyl 6-(cyclopentylmethylene)-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate

生成物 1

HCID 66722631methyl 2-(3-(benzyloxy)-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate収率 96%

試薬・触媒・溶媒 2

HCID 313Hydrochloric Acid触媒HCID 702Ethanol溶媒

反応条件

温度
80 °C

実験手順

A mixture of 2-(benzyloxy)-4-hydrazinylbenzonitrile; Preparation 13 (358 mg, 1.5 mmol), Methyl 6-(cyclopentylmethylene)-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate; Preparation 18 (284 mg, 1.0 mmol), ethanol (7 mL), and 1 drop of concentrated hydrogen chloride was stirred under argon at 80° C. for 64 hours. The mixture was cooled to room temperature, concentrated and purified by normal phase flash column chromatography on a 40 g silica gel column (20-80% ethyl acetate/hexanes gradient). Pure fractions were pooled and concentrated in vacuo to yield methyl 2-(3-(benzyloxy)-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate (yellow foam, 485 mg, 0.96 mmol, 96% yield). The title compound was largely present as (±)-(3RS,3aSR)-methyl 2-(3-(benzyloxy)-4-cyanophenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.00-1.51 (m, 7H), 1.56-1.68 (m, 1H), 1.82 (ddd, J=25.85, 12.96, 3.89 Hz, 1H), 1.95-2.08 (m, 1H), 2.15-2.31 (m, 1H), 2.82-2.95 (m, 1H), 3.11 (d, J=16.38 Hz, 1H), 3.53-3.63 (m, 1H), 3.87 (s, 3H), 4.91 (dd, J=9.53, 5.50 Hz, 1H), 5.31 (q, J=12.35 Hz, 2H), 6.85 (d, J=8.32 Hz, 1H), 6.96 (s, 1H), 7.35 (t, J=7.25 Hz, 1H), 7.39-7.57 (m, 5H), 7.80-7.92 (m, 2H), 8.10 (d, J=8.32 Hz, 1H). ES-MS m/z 506 (M+H).

後処理

  1. temperatureThe mixture was cooled to room temperature
  2. concentrationconcentrated
  3. custompurified by normal phase flash column chromatography on a 40 g silica gel column (20-80% ethyl acetate/hexanes gradient)
  4. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-ec04596dd8f143338437608f5e74719b
出典データセット
uspto-grants-2010_08
特許番号
US07781428B2

反応ノート

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