Dimethylformamide → HCID 44242579, compound

HRID 2408600Notes

Reaction equation

HRID 2408600 reaction equation
CN1C[CH2:14][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[H-].[Na+].[O:18]1[CH2:20][CH:19]1[C:21]1[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=1.[CH3:27][N:28](C=O)[CH3:29]>>[CH3:27][N:28]1[CH2:29][CH2:3][C:4]2[C:12]3[C:7](=[CH:8][CH:9]=[C:10]([CH3:13])[CH:11]=3)[N:6]([CH2:20][CH:19]([C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)[OH:18])[C:5]=2[CH2:14]1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 2092911H-Pyrido[4,3-b]indole, 2,3,4,5-tetrahydro-2,8-dimethyl-HCID 133195613-(Oxiran-2-yl)pyridine

Product 1

HCID 44242579HCID 44242579, compound

Procedure

To a solution of 2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1 g, 5 mmol) in 10 mL DMF, was added sodium hydride (600 mg, 15 mmol) portionwise under nitrogen at 0° C. and stirred for 10 min. 3-Oxiranyl-pyridine (908 mg, 15.0 mmol) was added dropwise under nitrogen and the reaction mixture stirred at RT for 12 h. After the complete conversion of starting material (TLC and LCMS), the reaction mixture was poured in ice-cold water and extracted with EtOAc (2×100 mL). The combined organic layer was washed with water (5×50 mL), dried over anhydrous sodium sulfate, and concentrated. The crude mixture was purified by reverse phase chromatography to obtain 290 mg of 2-(2,6-dimethyl-1,2,3,4-tetrahydro-β-carbolin-9-yl)-1-pyridin-3-yl-ethanol. 1H NMR (CDCl3, freebase) δ (ppm): 8.62 (s, 1H), 8.57 (d, 1H), 7.67 (d, 1H), 7.3 (m, 2H), 7.19 (d, 1H), 7.01 (d, 1H), 5.09 (t, 1H), 4.13 (m, 2H), 3.70 (d, 1H), 3.36 (d, 1H), 2.79 (m, 3H), 2.703 (m, 1H), 2.5 (s, 3H), 2.45 (s, 3H). Separation by chiral HPLC provided enantiomers 43a and 43b.

Workup

  1. stirringthe reaction mixture stirred at RT for 12 h
  2. additionAfter the complete conversion of starting material (TLC and LCMS), the reaction mixture was poured in ice-cold water
  3. extractionextracted with EtOAc (2×100 mL)
  4. washThe combined organic layer was washed with water (5×50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe crude mixture was purified by reverse phase chromatography

Sources & evidence

ORD record
ord-63c2c2635546414fac71dcb3013f6a66
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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