Sodium hydride → HCID 68283714, compound

HRID 2408612Notes

Reaction equation

HRID 2408612 reaction equation
[CH3:1][N:2]1[CH2:15][C:14]([CH3:17])([CH3:16])[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:20]1[CH2:22][CH:21]1[C:23]1[CH:28]=[CH:27][N:26]=[CH:25][CH:24]=1>CN(C=O)C>[N:26]1[CH:27]=[CH:28][C:23]([CH:21]([OH:20])[CH2:22][N:6]2[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]3[CH2:3][N:2]([CH3:1])[CH2:15][C:14]([CH3:17])([CH3:16])[C:5]2=3)=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 109534834-(Oxiran-2-yl)pyridineHCID 68283922HCID 68283922, compound

Product 1

HCID 68283714HCID 68283714, compoundYield 58.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2,4,4,8-Tetramethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1.0 gm, 4.385 mmol) was dissolved in DMF (8 mL) and sodium hydride (0.526 g, 13.15 mmol) was added portionwise under nitrogen. 4-Oxiranyl-pyridine (0.9 g, 7.45 mmol) was diluted in DMF (2 mL) and added dropwise at RT and stirred for 4 h. After consumption of starting material (by monitoring TLC & LCMS), the reaction mixture was poured in to ice water, product was precipitated and filtered, and the residue was washed with water & hexane, dried under reduced pressure and crystallized in EtOH (10 mL) and diethyl ether (50 mL) to obtain 900 mg of 1-pyridin-4-yl-2-(2,4,4,8-tetramethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-ethanol. 1H NMR (CDCl3, freebase) δ (ppm): 8.62 (d, 2H), 7.37 (d, 2H), 7.31 (d, 1H), 7.19 (s, 1H), 7.01 (d, 1H), 5.22 (t, 1H), 4.32 (d, 1H), 3.6 (d, 1H), 3.48 (d, 1H), 2.65 b(s, 1H), 2.44 (s, 3H), 1.47 (s, 3H), 1.28 (s, 3H). Separation by chiral HPLC provides enantiomers 71a and 71b.

Workup

  1. additionadded dropwise at RT
  2. customAfter consumption of starting material (by monitoring TLC & LCMS)
  3. additionthe reaction mixture was poured in to ice water, product
  4. customwas precipitated
  5. filtrationfiltered
  6. washthe residue was washed with water & hexane
  7. customdried under reduced pressure
  8. customcrystallized in EtOH (10 mL)

Sources & evidence

ORD record
ord-bdf4362d35864ce8b9d3d311e985b8f7
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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