Sodium hydride → 1-(9-chloro-2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-2-(pyridin-3-yl)propan-2-ol

HRID 2408709Notes

Reaction equation

HRID 2408709 reaction equation
[Cl:1][C:2]1[C:3]2[C:4]3[CH2:15][N:14]([CH3:16])[CH2:13][CH2:12][C:5]=3[NH:6][C:7]=2[CH:8]=[CH:9][C:10]=1[CH3:11].ClC1C(C)=CC2C3CN(C)CCC=3NC=2C=1.[H-].[Na+].[CH3:35][C:36]1([C:39]2[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=2)[CH2:38][O:37]1>CN(C=O)C>[Cl:1][C:2]1[C:3]2[C:4]3[CH2:15][N:14]([CH3:16])[CH2:13][CH2:12][C:5]=3[N:6]([CH2:35][C:36]([C:39]3[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=3)([OH:37])[CH3:38])[C:7]=2[CH:8]=[CH:9][C:10]=1[CH3:11]

Participants

6

Reactant 4

HCID 24758Sodium hydrideHCID 230811803-(2-Methyloxiran-2-yl)pyridineHCID 682838737-chloro-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoleHCID 682839539-chloro-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 682833251-(9-chloro-2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-2-(pyridin-3-yl)propan-2-ol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 9-chloro-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole and 7-chloro-2,8-dimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (2.00 g, 8.5 mmol) was dissolved in DMF (15 mL). Sodium hydride (1.708 g, 42.71 mmol) was added at 0-10° C. and stirred at the same temperature for 15 min., 3-(2-methyloxiran-2-yl)pyridine (2.309 g, 17.08 mmol) was added dropwise into the reaction mixture and the mixture was stirred at RT for 16 h. The reaction was monitored by TLC and LCMS. After consumption of starting material, the reaction mixture was quenched with ice cold water (100 mL) and extract with EtOAc (300 mL). The organic layer was washed with water (5×100 mL). The organic layer dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain the crude. The crude product was purified by reverse phase column chromatography to obtain 35 mg of 1-(9-chloro-2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-2-(pyridin-3-yl)propan-2-ol. 1H NMR (CD3OD, freebase) δ (ppm): 8.46 (s, 1H), 8.34 (d, 1H), 7.82 (d, 1H), 7.29 (t, 1H), 6.87 (d, 1H), 6.77 (d, 1H), 4.22 (dd, 2H), 3.99 (q, 2H), 2.73 (m, 4H), 2.5 (s, 3H), 2.3 (s, 3H), 1.66 (s, 3H). Separation by chiral HPLC provided enantiomers II-124a-b.

Workup

  1. stirringthe mixture was stirred at RT for 16 h
  2. customAfter consumption of starting material
  3. customthe reaction mixture was quenched with ice cold water (100 mL)
  4. extractionextract with EtOAc (300 mL)
  5. washThe organic layer was washed with water (5×100 mL)
  6. dry with materialThe organic layer dried over anhydrous sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customto obtain the crude
  9. customThe crude product was purified by reverse phase column chromatography

Sources & evidence

ORD record
ord-68892ace6ee848fc9c535dce67fc9f02
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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