Sulfuric Acid → 2,3,8-trimethyl-5-(2-(6-methylpyridin-3-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

HRID 1773251Notes

Reaction equation

[CH3:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)N)=[CH:4][CH:3]=1.[CH3:19][N:20]1[CH2:25][CH2:24][C:23](=O)[CH2:22][CH:21]1[CH3:27].S(=O)(=O)(O)O.C([O-])(O)=O.[Na+]>O1CCOCC1>[CH3:19][N:20]1[CH:21]([CH3:27])[CH2:22][C:23]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:17]=[CH:16][C:15]([CH3:18])=[CH:14][C:13]=3[C:24]=2[CH2:25]1

Participants

Conditions

Temperature: 85 °C

Procedure

To a solution of N-[2-(6-methyl-pyridin-3-yl)-ethyl]-N-p-tolyl-hydrazine (200 mg, 0.829 mmol) in dioxane (7 mL) was added 1,2-dimethyl-piperidin-4-one (137 mg, 1.078 mmol) in dioxane (3 mL) at RT. To this mixture was added sulfuric acid (0.1 mL) at RT. After complete addition the mixture was stirred at 85° C. for 1 h. The reaction was monitored by TLC. After completion of reaction, the mixture was basified with NaHCO3 solution and extracted with EtOAc (300 mL). The organic layer was dried over sodium sulfate, concentrated under vacuum and purified by HPLC to obtain 28.5 mg of desired compound as the TFA salt. 1HNMR (CD3OD, TFA salt) d (ppm): 8.20 (s, 1H), 8.05 (d, 1H), 7.63 (d, 1H), 7.25 (s, 1H), 7.10 (d, 1H), 6.95 (d, 1H), 4.70 (m, 1H), 4.45 (t, 2H), 4.36 (m, 1H), 4.05 (m, 1H), 3.75 (m, 1H), 3.20 (m, 2H), 3.0 (m, 3H), 2.90 (m, 1H), 2.62 (s, 3H), 2.40 (s, 3H), 1.50 (d, 3H).

Workup

additionAfter complete addition the mixture
customAfter completion of reaction
extractionextracted with EtOAc (300 mL)
dry with materialThe organic layer was dried over sodium sulfate
concentrationconcentrated under vacuum
custompurified by HPLC

Sources & evidence

ORD record: ord-56be502684a3405fbfc1b24c6650e632
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09255094B2

Reaction notes

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