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

HRID 1469559Notes

Reaction equation

HRID 1469559 reaction equation
[CH3:1][N:2]1[CH2:16][CH2:15][C:5]2[NH:6][C:7]3[CH:8]=[CH:9][C:10]([CH3:14])=[C:11]([CH3:13])[C:12]=3[C:4]=2[CH2:3]1.[H-].[Na+].[CH3:19][C:20]1([C:23]2[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=2)[CH2:22][O:21]1>CN(C=O)C>[N:25]1[CH:26]=[CH:27][CH:28]=[C:23]([C:20]([OH:21])([CH3:22])[CH2:19][N:6]2[C:7]3[CH:8]=[CH:9][C:10]([CH3:14])=[C:11]([CH3:13])[C:12]=3[C:4]3[CH2:3][N:2]([CH3:1])[CH2:16][CH2:15][C:5]2=3)[CH:24]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 230811803-(2-Methyloxiran-2-yl)pyridineHCID 682843422,8,9-Trimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

Product 1

HCID 682832292-(pyridin-3-yl)-1-(2,8,9-trimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)propan-2-olYield 61.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2,8,9-Trimethyl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole (400 mg, 1.86 mmol) 4 mL DMF, cooled to 0° C. and sodium hydride (224 mg, 5.60 mmol) was added portionwise at the same temperature. 3-(2-methyloxiran-2-yl)pyridine (504 mg, 3.73 mmol) in DMF (1 mL) was added to the reaction mixture and allowed to stir at RT for 12 h. After complete consumption of starting material, the reaction mixture was poured in to ice water and extracted with EtOAc (3×100 mL). The combined organic layer was washed with water (3×50 mL), dried over anhydrous sodium sulfate and concentrated to obtain the crude product, which was crystallized with ether and hexane to obtain 400 mg of 2-(pyridin-3-yl)-1-(2,8,9-trimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)propan-2-ol. 1H NMR (DMSO, freebase) δ (ppm): 8.59 (s, 1H), 8.42 (d, 1H), 7.73 (d, 1H), 7.31 (t, 1H), 7.1 (d, 1H), 6.73 (d, 1H), 4.11 (dd, 2H), 3.74 (s, 2H), 3.4 (m, 2H), 2.6 (m, 2H), 2.37 (s, 6H), 2.22 (s, 3H), 1.5 (s, 3H). Separation by chiral HPLC provides enantiomers II-145a-b.

Workup

  1. customAfter complete consumption of starting material
  2. additionthe reaction mixture was poured in to ice water
  3. extractionextracted with EtOAc (3×100 mL)
  4. washThe combined organic layer was washed with water (3×50 mL)
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customto obtain the crude product, which
  8. customwas crystallized with ether and hexane

Sources & evidence

ORD record
ord-335bdbf96e404ab1b2e2b8e6ca711359
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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