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 2195870Notes

Reaction equation

[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

Participants

Conditions

Temperature: 100 °C

Procedure

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. 1 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×10 μFlow: 301 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×4.6×3.5μ), 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 S min. number of injections: 25 Purity of pooled fraction: 98% Collected fractions were lyophilized Purity after lyophilization: 92.07%

Workup

concentrationThe reaction mixture was concentrated
custompurified by reverse phase

Sources & evidence

ORD record: ord-aef1beb9ec1b4d53b1aa8b38ed661de9
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08338408B2

Reaction notes

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