Ethyl bromoacetate → 2-((1-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-2-(pyridin-3-yl)propan-2-yl)oxy)acetic acid

HRID 1630654Notes

Reaction equation

HRID 1630654 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.C(=O)([O-])[O-].[K+].[K+].Br[CH2:33][C:34]([O:36]CC)=[O:35]>CN(C=O)C>[CH3:1][N:2]1[CH2:25][CH2:24][C:5]2[N:6]([CH2:14][C:15]([O:17][CH2:33][C:34]([OH:36])=[O:35])([C:18]3[CH:19]=[N:20][CH:21]=[CH:22][CH:23]=3)[CH3:16])[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 7748Ethyl bromoacetateHCID 11430Potassium CarbonateHCID 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 682830592-((1-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-2-(pyridin-3-yl)propan-2-yl)oxy)acetic acidYield 34.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-2-(pyridin-3-yl)propan-2-ol (200 mg, 0.597 mmol) in DMF (5 mL) was added potassium carbonate (412 mg, 2.98 mmol). After stirring for 5 min at RT, ethyl bromoacetate (200 mg, 1.19 mmol) was added into the reaction mixture, which was stirred at RT for 2 h. The progress of reaction was monitored by LCMS. The reaction was quenched with water and extracted with EtOAc. The aqueous layer was concentrated and residue was purified by reverse HPLC to yield 2-((1-(2,8-dimethyl-3,4-dihydro-1H-pyrido[4,3-b]indol-5(2H)-yl)-2-(pyridin-3-yl)propan-2-yl)oxy)acetic acid (80 mg). The resulting racemate was purified and resolved by chiral preparative HPLC. 1H NMR (CD3OD, freebase) δ (ppm): 8.5 (d, 1H), 8.36 (s, 1H), 7.8 (dd, 1H), 7.31 (m, 1H), 7.19 (s, 1H), 7.1 (d, 1H), 6.88 (d, 1H), 4.86 (m, 1H), 4.58 (s, 1H), 4.32 (d, 1H), 4.25 (m, 2H), 3.94 (m, 2H), 3.8 (m, 1H), 3.35 (s, 3H), 3.2 (m, 1H), 3.0 (m, 1H), 2.36 (s, 3H), 1.69 (s, 3H).

Workup

  1. stirringwas stirred at RT for 2 h
  2. customThe progress of reaction
  3. customThe reaction was quenched with water
  4. extractionextracted with EtOAc
  5. concentrationThe aqueous layer was concentrated
  6. customresidue was purified by reverse HPLC

Sources & evidence

ORD record
ord-c50d30b2856c4376a33e3627be5cf642
Source dataset
uspto-grants-2014_07
Patent number
US08791132B2

Reaction notes

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