Sodium hydride → 2,2-Dimethyl-propionic acid 2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-methyl-1-pyridin-3-yl-ethyl ester

HRID 1469516Notes

Reaction equation

HRID 1469516 reaction equation
[CH3:1][N:2]1[CH2:25][CH2:24][C:5]2[N:6]([CH2:14][C:15]([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)([OH:17])[CH3:16])[C:7]3[CH:8]=[CH:9][C:10]([CH3:13])=[CH:11][C:12]=3[C:4]=2[CH2:3]1.[H-].[Na+].[C:28](Cl)(=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30]>CN(C=O)C>[CH3:1][N:2]1[CH2:25][CH2:24][C:5]2[N:6]([CH2:14][C:15]([O:17][C:28](=[O:33])[C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:16])[C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[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 62493Pivaloyl chlorideHCID 578760881-(1,2,3,4-Tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)-2-(pyridin-3-yl)propan-2-ol

Product 1

HCID 682837152,2-Dimethyl-propionic acid 2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-methyl-1-pyridin-3-yl-ethyl esterYield 28.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

1-(2,8-Dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-2-pyridin-3-yl-propan-2-ol (5.0 g, 14.9 mmol) was dissolved in DMF (100 mL) and sodium hydride (1.8 g, 45 mmol) was added, and the mixture stirred at RT for 15 min. Pivaloyl chloride (3 g, 25 mmol) was added dropwise at the same temperature, and the mixture stirred for 45 min. The reaction was monitored by TLC and LCMS. The reaction mixture was poured into 400 mL ice water to obtain a solid that was filtered. The solid was dissolved in DCM, dried over sodium sulfate and concentrated to obtain the crude product that was purified by column chromatography (silica gel: 100-200 mesh, Eluent: −4-6% MeOH in DCM) to obtain 1.8 g of 2,2-dimethyl-propionic acid 2-(2,8-dimethyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-methyl-1-pyridin-3-yl-ethyl ester. The product was further purified by chiral preparative HPLC to give enantiomers II-16a and II-16b. 1H NMR (CDCl3, Free base): δ (ppm): 8.55 (d, 1H), 8.5 (s, 1H), 7.2 (d, 1H), 7.18 (m, 3H), 6.9 (d, 1H), 4.3 (dd, 2H), 3.65 (d, 1H), 3.52 (d, 1H), 2.65 (m, 2H), 2.5 (m, 2H), 2.5 (s, 3H), 2.4 (s, 3H), 2.3 (d, 1H), 2.0 (s, 3H), 2.0 (m, 1H), 1.2 (s, 9H).

Workup

  1. stirringthe mixture stirred for 45 min
  2. customto obtain a solid
  3. filtrationthat was filtered
  4. dissolutionThe solid was dissolved in DCM
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customto obtain the crude product that
  8. customwas purified by column chromatography (silica gel: 100-200 mesh, Eluent: −4-6% MeOH in DCM)

Sources & evidence

ORD record
ord-b2f05c7c7a03451e8504abeeaed4d208
Source dataset
uspto-grants-2015_04
Patent number
US09006263B2

Reaction notes

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