1-Methyl-4-piperidone → 2-Methyl-5-(2-(6-methylpyridin-3-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxylic acid

HRID 574426노트

반응식

HRID 574426 반응식
[CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]([C:12]2[CH:21]=[CH:20][C:15]([C:16]([O:18]C)=[O:17])=[CH:14][CH:13]=2)N)=[CH:4][CH:3]=1.[CH3:22][N:23]1[CH2:28][CH2:27][C:26](=O)[CH2:25][CH2:24]1>Cl>[CH3:22][N:23]1[CH2:28][CH2:27][C:26]2[N:10]([CH2:9][CH2:8][C:5]3[CH:6]=[N:7][C:2]([CH3:1])=[CH:3][CH:4]=3)[C:12]3[CH:21]=[CH:20][C:15]([C:16]([OH:18])=[O:17])=[CH:14][C:13]=3[C:25]=2[CH2:24]1

참가 물질

4

반응물 2

HCID 740491-Methyl-4-piperidoneHCID 68735268Methyl 4-(1-(2-(6-methylpyridin-3-yl)ethyl)hydrazinyl)benzoate

생성물 1

HCID 578760502-Methyl-5-(2-(6-methylpyridin-3-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxylic acid수율 4.1%

시약·촉매·용매 1

HCID 313Hydrochloric Acid용매

반응 조건

온도
100 °C

실험 절차

Methyl 4-(1-(2-(6-methylpyridin-3-yl)ethyl)hydrazinyl)benzoate (0.1 g, 0.350 mmoles) and 1-methylpiperidin-4-one (0.052 g, 0.350 mmoles) was taken up in 4 mL 1M HCl and heated at 100 degrees C. for 18 hr. LCMS of the reaction mixture shows the formation of the product. The reaction mixture was concentrated and purified by reverse phase HPLC.1 to give 5 mg of 2-Methyl-5-(2-(6-methylpyridin-3-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-8-carboxylic acid, as a white solid, 4% yield. Batch Size—800 mg, Purity:—˜3% Since the compound is highly Polar First Purification Was carried on prep HPLC using Water (0.05% TFA) as eluent. Method Details: Sample preparation: Compound dissolved in Milli-Q Water (4.0 mL) Clear Brown solution Column: YMC ODS A, 500 mm×30 mm×10μ Flow: 30 mL/min Wavelength: monitored at 220 nm & 254 nm. Mobile Phase Mobile Phase A: 0.05% TFA in water Mobile Phase B: 0.05% TFA in Acetonitrile Gradient Program 0% B for 15 min 0% B to 50% B in 27 min. Column Washed with 100% methanol. Collected fractions were lyophilized. Lyophilized solid having purity 80% were dissolved in 250 μL and analyzed by following method. (Method details for analysis: Column Zorbax cyano, 150 mm×4.6×3.50, Flow: 1.2 mL/min, inj. Vol: 10.0 μL, Wavelength: 220 nm & 254 nm, Gradient Program: 0% B to 50% B in 5 min hold for 2 min 7.01 min to 10.0 min 0% B Second purification Total Vol: 250 μL Column: Zorbax cyano, 150 mm×4.6×3.5μ), Flow: 1.2 mL/min, inj. Vol: 10.0 μL, Wavelength: 220 nm & 254 nm, Mobile Phase Mobile Phase A: 0.05% TFA in water Mobile Phase B: 0.05% TFA in Acetonitrile Isocratic program 8% B for 5 min. number of injections: 25 Purity of pooled fraction: 98% Collected fractions were lyophilized Purity after lyophilization: 92.07%

후처리

  1. concentrationThe reaction mixture was concentrated
  2. custompurified by reverse phase

출처 및 근거

ORD 기록
ord-e4c83969408e44b4a4507db669f88ddc
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09034880B2

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