Sodium hydride → HCID 60197172, compound

HRID 1469438Notes

Reaction equation

HRID 1469438 reaction equation
[CH3:1][N:2]1[CH2:15][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+].[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([CH:26]2[CH2:28][O:27]2)=[CH:22][N:21]=1>CN(C=O)C>[CH3:1][N:2]1[CH2:15][CH2:14][C:5]2[N:6]([CH2:28][CH:26]([C:23]3[CH:22]=[N:21][C:20]([O:19][CH3:18])=[CH:25][CH:24]=3)[OH:27])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 2092911H-Pyrido[4,3-b]indole, 2,3,4,5-tetrahydro-2,8-dimethyl-HCID 59261579HCID 59261579, compound

Product 1

HCID 60197172HCID 60197172, compoundYield 56.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

2,8-Dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (1.0 g, 5.0 mmol) was dissolved in DMF (8 mL). Sodium hydride (600 mg, 15 mmol) was added portionwise under nitrogen at 0° C. 2-Methoxy-5-oxiranyl-pyridine (1.130 g, 7.5 mmol) was diluted in DMF (2 mL) was added dropwise under nitrogen atmosphere and the reaction mixture stirred at RT for 3 h. By monitoring TLC & NMR after consumption of starting material, the reaction mixture was then quenched with ice water and extracted with EtOAc (3×40 mL). The combined organic layer was washed with water (4×30 mL) and dried over anhydrous sodium sulfate and concentrated to obtain 1.0 g of 2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-(6-methoxy-pyridin-3-yl)-ethanol. 1H NMR (CDCl3, freebase) δ (ppm): 8.11 (s, 1H), 7.55 (d, 1H), 7.18 (s, 1H), 7.16 (d, 1H), 6.98 (d, 1H), 6.72 (d, 1H), 4.98 (t, 1H), 4.11 (m, 2H), 3.93 (s, 3H), 3.60 (q, 2H), 2.88 (d, 1H), 2.78 (m, 2H), 2.69 (d, 1H), 2.51 (s, 3H), 2.44 (s, 3H). Separation by chiral HPLC provided enantiomers 51a and 51b.

Workup

  1. additionwas added dropwise under nitrogen atmosphere
  2. customafter consumption of starting material
  3. customthe reaction mixture was then quenched with ice water
  4. extractionextracted with EtOAc (3×40 mL)
  5. washThe combined organic layer was washed with water (4×30 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-cda2647d2a984595919b7a646ce09aa2
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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