2-Bromoethanol → HCID 60197484, compound

HRID 2408685Notes

Reaction equation

HRID 2408685 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:8]2[N:7]([CH2:11][CH:12]([C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[OH:13])[C:6]3[CH2:20][CH2:21][NH:22][CH2:23][C:5]=3[C:4]=2[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:31][CH2:32][OH:33]>C(#N)C.O>[OH:33][CH2:32][CH2:31][N:22]1[CH2:21][CH2:20][C:6]2[N:7]([CH2:11][CH:12]([C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[OH:13])[C:8]3[CH:9]=[CH:10][C:2]([CH3:1])=[CH:3][C:4]=3[C:5]=2[CH2:23]1

Participants

6

Reactant 3

HCID 108982-BromoethanolHCID 11430Potassium CarbonateHCID 68284096HCID 68284096, compound

Product 1

HCID 60197484HCID 60197484, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of 2-(8-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl)-1-pyridin-4-yl-ethanol (100 mg, 0.325 mmol) in acetonitrile (3 mL), potassium carbonate (135 mg, 0.977 mmol) and 2-bromoethanol (61 mg, 0.488 mmol) were added and the reaction mixture stirred at 60° C. for 1 h. The progress of reaction was monitored by TLC and LCMS. The reaction mixture was diluted with water (10 mL) and extracted with EtOAc (3×20 mL). The combined organic layer was dried over anhydrous sodium sulfate and concentrated. The residue was purified by reverse phase HPLC to yield 2-[2-(2-hydroxy-ethyl)-8-methyl-1,2,3,4-tetrahydro-pyrido[4,3-b]indol-5-yl]-1-pyridin-4-yl-ethanol. 1H NMR (CD3OD, formate salt) δ (ppm): 8.41 (d, 2H), 7.38 (d, 2H), 7.2 (m, 2H), 6.99 (d, 1H), 5.03 (t, 1H), 4.4 (bs, 2H), 4.3 (d, 2H), 3.93 (t, 2H), 3.45-3.62 (m, 2H), 3.2 (m, 2H), 2.9 (m, 2H), 2.4 (s, 3H). Separation by chiral HPLC provides enantiomers II-64a-b.

Workup

  1. customThe progress of reaction
  2. extractionextracted with EtOAc (3×20 mL)
  3. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-9818d2500ffe45d19e5c2316866ecb15
Source dataset
uspto-grants-2014_08
Patent number
US08815843B2

Reaction notes

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