Ethyl bromoacetate → HCID 68283792, compound

HRID 1630583Notes

Reaction equation

HRID 1630583 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+].[CH2:30]([O:32][C:33](=[O:36])[CH2:34]Br)[CH3:31]>C(#N)C.O>[CH2:30]([O:32][C:33](=[O:36])[CH2:34][N:22]1[CH2:21][CH2:20][C:6]2[N:7]([CH2:11][CH:12]([OH:13])[C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[C:8]3[CH:9]=[CH:10][C:2]([CH3:1])=[CH:3][C:4]=3[C:5]=2[CH2:23]1)[CH3:31]

Participants

6

Reactant 3

HCID 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 68284096HCID 68284096, compound

Product 1

HCID 68283792HCID 68283792, compoundYield 85.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

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 (200 mg, 0.651 mmol) in acetonitrile (4 mL), potassium carbonate (270 mg, 1.953 mmol) and bromo-acetic acid ethyl ester (163 mg, 0.977 mmol) were added and the reaction mixture was stirred at RT 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 (3×30 mL). The combined organic layer was dried over anhydrous sodium sulfate and concentrated to yield [5-(2-hydroxy-2-pyridin-4-yl-ethyl)-8-methyl-1,3,4,5-tetrahydro-pyrido[4,3-b]indol-2-yl]-acetic acid ethyl ester (220 mg). To a solution of [5-(2-hydroxy-2-pyridin-4-yl-ethyl)-8-methyl-1,3,4,5-tetrahydro-pyrido[4,3-b]indol-2-yl]-acetic acid ethyl ester (120 mg, 0.305 mmol) in ethanol (2 mL), 1N NaOH (3 mL) was added and the reaction mixture stirred at RT for 1 h. The progress of reaction was monitored by LCMS. The reaction mixture was neutralized with aq HCl. The solvent was removed under reduced pressure and the residue diluted with 90% MeOH in DCM and filtered. The filtrate was concentrated and residue was purified by reverse phase HPLC to yield [5-(2-hydroxy-2-pyridin-4-yl-ethyl)-8-methyl-1,3,4,5-tetrahydro-pyrido[4,3-b]indol-2-yl]-acetic acid. 1H NMR (CD3OD, formate salt) δ (ppm): 8.42 (d, 2H), 7.4 (d, 2H), 7.2 (d, 2H), 6.9 (d, 1H), 5.03 (t, 1H), 4.6 (bs, 1H), 4.57 (bs, 2H), 4.3 (m, 2H), 3.8 (s, 2H), 3.7 (bs, 2H), 3.0 (m, 1H), 2.3 (s, 3H). Separation by chiral HPLC provides enantiomers II-65a-b.

Workup

  1. customThe progress of reaction
  2. extractionextracted with EtOAc (3×30 mL)
  3. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-200964b1d0284a03a1dcc1f0bbf48af7
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

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