Water → HCID 60197076, compound

HRID 1469436Notes

Reaction equation

HRID 1469436 reaction equation
[H-].[Na+].[CH3:3][O:4][C:5]1[C:13]2[NH:12][C:11]3[CH2:14][CH2:15][N:16]([CH3:18])[CH2:17][C:10]=3[C:9]=2[CH:8]=[CH:7][CH:6]=1.[O:19]1[CH2:21][CH:20]1[C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1.O>CN(C=O)C>[CH3:3][O:4][C:5]1[C:13]2[N:12]([CH2:21][CH:20]([C:22]3[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=3)[OH:19])[C:11]3[CH2:14][CH2:15][N:16]([CH3:18])[CH2:17][C:10]=3[C:9]=2[CH:8]=[CH:7][CH:6]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 109534834-(Oxiran-2-yl)pyridineHCID 545884621253640-41-3

Product 1

HCID 60197076HCID 60197076, compoundYield 10.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60%) (555 mg, 13.88 mmol) was added portionwise to a solution of 6-methoxy-2-methyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1.0 g, 4.629 mmol) in DMF (10 mL) and stirred at RT for 15 min, the suspension was allowed to cool at 0° C. 4-(Oxiran-2-yl)pyridine (896 mg, 7.407 mmol) was added dropwise and reaction mixture was stirred at RT for 48 h. The reaction mixture was poured in to ice-cooled water and extracted with EtOAc (3×50 mL), and the organic layer was washed with water (2×50 mL), dried over anhydrous sodium sulfate and concentrated in vacuo, afforded crude was purified by reverse phase HPLC to afford 2-(6-methoxy-2-methyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-1-(pyridin-4-yl)ethanol (165 mg) as the formate salt. 1H NMR (CDCl3, freebase) δ (ppm): 8.60 (d, 2H), 7.31 (d, 2H), 7.02 (m, 2H), 6.66 (d, 1H), 5.08 (dd, 1H), 4.66 (dd, 1H), 4.12 (dd, 1H), 3.99 (s, 3H), 3.60 (d, 1H), 3.56 (d, 1H), 2.9 (m, 1H), 2.81 (m, 1H), 2.72 (m, 1H), 2.64 (m, 1H), 2.55 (s, 3H). Separation by chiral HPLC provided enantiomers 44a and 44b.

Workup

  1. temperatureto cool at 0° C
  2. customreaction mixture
  3. stirringwas stirred at RT for 48 h
  4. additionThe reaction mixture was poured in to ice-
  5. extractionextracted with EtOAc (3×50 mL)
  6. washthe organic layer was washed with water (2×50 mL)
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationconcentrated in vacuo
  9. customafforded crude
  10. customwas purified by reverse phase HPLC

Sources & evidence

ORD record
ord-204dbc58fc3c4c909ea05e07f6507adb
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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