Methanol → 2-(4-cyano-3-(methoxymethyl)phenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid

HRID 505724노트

반응식

HRID 505724 반응식
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:17]([CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[CH:16]3[C:11]([C:12]4[CH:26]=[CH:25][C:24]([C:27]([O:29]CC)=[O:28])=[CH:23][C:13]=4[CH2:14][CH2:15]3)=[N:10]2)=[CH:5][C:4]=1[CH2:32][O:33][CH3:34])#[N:2].CO.[OH-].[Na+]>O1CCCC1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]2[CH:17]([CH:18]3[CH2:19][CH2:20][CH2:21][CH2:22]3)[CH:16]3[C:11]([C:12]4[CH:26]=[CH:25][C:24]([C:27]([OH:29])=[O:28])=[CH:23][C:13]=4[CH2:14][CH2:15]3)=[N:10]2)=[CH:5][C:4]=1[CH2:32][O:33][CH3:34])#[N:2]

참가 물질

5

반응물 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 66722633ethyl 2-(4-cyano-3-(methoxymethyl)phenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylate

생성물 1

HCID 667225982-(4-cyano-3-(methoxymethyl)phenyl)-3-cyclopentyl-3,3a,4,5-tetrahydro-2H-benzo[g]indazole-7-carboxylic acid수율 18%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

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)

후처리

  1. concentrationAfter four hours the mixture was concentrated to half the original volume
  2. additiontreated with 6 N Hydrogen chloride (2 mL), dimethylsulfoxide (24 mL)
  3. custompurified by reversed-phase HPLC (acetonitrile/water/0.05% trifluoroacetic acid)

출처 및 근거

ORD 기록
ord-17f5d4d6e53640009508aed41011bd27
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07781428B2

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