Sodium hydride → 1-(7-chloro-2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-2-(pyridin-3-yl)propan-2-ol

HRID 1469544Notes

Reaction equation

HRID 1469544 reaction equation
ClC1C2C3CN(C)CCC=3NC=2C=CC=1C.[Cl:17][C:18]1[C:19]([CH3:32])=[CH:20][C:21]2[C:22]3[CH2:30][N:29]([CH3:31])[CH2:28][CH2:27][C:23]=3[NH:24][C:25]=2[CH:26]=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:17][C:18]1[C:19]([CH3:32])=[CH:20][C:21]2[C:22]3[CH2:30][N:29]([CH3:31])[CH2:28][CH2:27][C:23]=3[N:24]([CH2:35][C:36]([C:39]3[CH:40]=[N:41][CH:42]=[CH:43][CH:44]=3)([OH:37])[CH3:38])[C:25]=2[CH:26]=1

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 682837671-(7-chloro-2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-2-(pyridin-3-yl)propan-2-olYield 11.1%

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 350 mg of 1-(7-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, HCl salt) δ (ppm): 8.68 (m, 3H), 7.95 (m, 1H), 7.29 (d, 1H), 6.9 (m, 1H), 4.68 (dd, 1H), 4.38 (m, 2H), 4.32 (dd, 1H), 3.9 (m, 1H), 3.52 (m, 2H), 3.25 (m, 1H), 3.12 (s, 3H), 2.35 (d, 3H), 1.83 (d, 3H). Separation by chiral HPLC provided enantiomers II-123a-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-1ce2cf554d5648aca3394589ef6e7074
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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