Ethanol → ethyl 2-(4-cyano-3-(methoxymethyl)phenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate

HRID 505723

反応式

HRID 505723 の反応式
Cl.[NH:2]([C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[C:6]([CH2:12][O:13][CH3:14])[CH:5]=1)[NH2:3].[CH:15]1([CH:20]=[C:21]2[CH2:30][CH2:29][C:28]3[CH:27]=[C:26]([C:31]([O:33][CH3:34])=[O:32])[CH:25]=[CH:24][C:23]=3[C:22]2=O)[CH2:19][CH2:18][CH2:17][CH2:16]1.[CH2:36](O)C>>[C:8]([C:7]1[CH:10]=[CH:11][C:4]([N:2]2[CH:20]([CH:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)[CH:21]3[C:22]([C:23]4[CH:24]=[CH:25][C:26]([C:31]([O:33][CH2:34][CH3:36])=[O:32])=[CH:27][C:28]=4[CH2:29][CH2:30]3)=[N:3]2)=[CH:5][C:6]=1[CH2:12][O:13][CH3:14])#[N:9]

参加物

4

反応物 3

HCID 702EthanolHCID 469151914-Hydrazinyl-2-(methoxymethyl)benzonitrile hydrochlorideHCID 66722547Methyl 6-(cyclopentylmethylene)-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate

生成物 1

HCID 66722633ethyl 2-(4-cyano-3-(methoxymethyl)phenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate

反応条件

温度
80 °C

実験手順

A mixture of 4-hydrazinyl-2-(methoxymethyl)benzonitrile hydrochloride, Methyl 6-(cyclopentylmethylene)-5-oxo-5,6,7,8-tetrahydronaphthalene-2-carboxylate; Preparation 18 (209 mg, 0.73 mmol) and ethanol (4 mL) was stirred under argon at 80° C. for four hours. The mixture was cooled to room temperature and concentrated to give ethyl 2-(4-cyano-3-(methoxymethyl)phenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate as a yellow solid. The ester was suspended in tetrahydrofuran (4 mL), methanol (1 mL) and treated with 2.5 N sodium hydroxide (1 mL) at room temperature. After four hours the mixture was concentrated to half the original volume, treated with 6 N Hydrogen chloride (2 mL), dimethylsulfoxide (24 mL) and purified by reversed-phase HPLC (acetonitrile/water/0.05% trifluoroacetic acid) to give 2-(4-cyano-3-(methoxymethyl)phenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid (yellow/orange solid, 65 mg, 0.015 mmol, 18% yield). The title compound was largely present as (±)-(3RS,3aSR)-2-(4-cyano-3-(methoxymethyl)phenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.04 (s, 1H), 8.07 (d, J=8.06 Hz, 1H), 7.80-7.87 (m, 2H), 7.60 (d, J=8.86 Hz, 1H), 7.35 (d, J=2.15 Hz, 1H), 7.18 (dd, J=8.86, 2.15 Hz, 1H), 4.92 (dd, J=9.80, 5.51 Hz, 1H), 4.50 (s, 2H), 3.59 (ddd, J=13.83, 9.40, 4.70 Hz, 1H), 3.36 (s, 3H), 3.06-3.15 (m, 1H), 2.82-2.96 (m, 1H), 2.19-2.29 (m, 1H), 2.00-2.13 (m, 1H), 1.65-1.89 (m, 2H), 1.14-1.54 (m, 7H). ES-MS m/z 430 (M+H)

後処理

  1. temperatureThe mixture was cooled to room temperature
  2. concentrationconcentrated

出典と根拠

ORDレコード
ord-71d2ea5e305946f392f891c497f6df42
出典データセット
uspto-grants-2010_08
特許番号
US07781428B2

関連ノート

読み込み中…