Potassium Hydroxide → HCID 68284211, compound

HRID 1630620Notes

Reaction equation

HRID 1630620 reaction equation
Cl[C:2]1[C:7]([C:8]([OH:26])([CH3:25])[CH2:9][N:10]2[C:18]3[CH:17]=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=3[C:12]3[CH2:20][N:21]([CH3:24])[CH2:22][CH2:23][C:11]2=3)=[CH:6][CH:5]=[CH:4][N:3]=1.[OH-:27].[K+]>C(O)(C)(C)C.[Cl-].[Na+].O>[CH3:24][N:21]1[CH2:22][CH2:23][C:11]2[N:10]([CH2:9][C:8]([C:7]3[C:2](=[O:27])[NH:3][CH:4]=[CH:5][CH:6]=3)([OH:26])[CH3:25])[C:18]3[CH:17]=[CH:16][C:15]([CH3:19])=[CH:14][C:13]=3[C:12]=2[CH2:20]1

Participants

5

Reactant 2

HCID 14797Potassium HydroxideHCID 86677151HCID 86677151, compound

Product 1

HCID 68284211HCID 68284211, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 6386tert-ButanolSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
90 °C

Procedure

2-(2-Chloropyridin-3-yl)-1-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)propan-2-ol (100 mg, 0.277 mmol) and crushed potassium hydroxide (106 mg, 1.89 mmol) in 3 mL tert. butanol were heated at 90° C. for 4 h. The reaction mixture was monitored by TLC and LCMS. The reaction mixture was cooled at RT, diluted with 100 mL brine solution and extracted with EtOAc (3×100 mL). The combined organic layer was washed with brine (3×100 mL), dried over anhydrous sodium sulfate and concentrated to obtain the crude product, which was purified by reverse phase chromatography to get the 35 mg of 3-(1-(1,2,3,4-tetrahydro-2,8-dimethylpyrido[4,3-b]indol-5-yl)-2-hydroxypropan-2-yl)pyridin-2(1H)-one as the TFA salt. 1H NMR (CD3OD, TFA salt) δ (ppm): 7.79 (d, 1H), 7.35 (m, 2H), 7.17 (s, 1H), 6.93 (d, 1H), 6.34 (t, 1H), 4.61 (d, 2H), 4.3 (d, 2H), 3.9 (m, 1H), 3.8 (m, 1H), 3.36 (m, 2H), 3.1 (s, 3H), 2.37 (s, 3H), 1.51 (s, 3H). Separation by chiral HPLC provides enantiomers II-143a-b.

Workup

  1. temperatureThe reaction mixture was cooled at RT
  2. extractionextracted with EtOAc (3×100 mL)
  3. washThe combined organic layer was washed with brine (3×100 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated
  6. customto obtain the crude product, which
  7. customwas purified by reverse phase chromatography

Sources & evidence

ORD record
ord-bfe21edc6545479294dc7a5b44769c37
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

Loading…