Ethyl Acetate → HCID 58215649, compound

HRID 593552Notes

Reaction equation

HRID 593552 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[NH:8][C:9]3[C:14]([CH:15]=2)=[CH:13][C:12]([C:16]#[N:17])=[CH:11][CH:10]=3)[CH:2]=1.CC(C)([O-])C.[K+].[CH3:24][C:25]([CH3:31])([CH3:30])[C:26](=[O:29])[CH:27]=[CH2:28].C(OCC)(=O)C>CS(C)=O.Cl.C(OCC)C>[CH3:24][C:25]([CH3:31])([CH3:30])[C:26](=[O:29])[CH2:27][CH2:28][N:8]1[C:9]2[C:14](=[CH:13][C:12]([C:16]#[N:17])=[CH:11][CH:10]=2)[CH:15]=[C:7]1[C:3]1[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=1

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 30140801-Penten-3-one, 4,4-dimethyl-HCID 23665647Potassium tert-butoxideHCID 445541352-pyridin-3-yl-1H-indole-5-carbonitrile

Product 1

HCID 58215649HCID 58215649, compound

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidCatalystHCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of 2-pyridin-3-yl-1H-indole-5-carbonitrile (Example 8, 0.225 g, 1.026 mmol) in DMSO (5 mL) is added potassium tert-butoxide (0.182 g, 1.53 mmol) and the mixture is stirred at room temperature for 0.5 h. 4,4-Dimethyl-pent-1-en-3-one (0.345 g, 3.078 mmol) is added and the mixture is stirred at 50° C. overnight. Dilution with ethyl acetate gives a solution which is washed with water twice, dried over sodium sulfate and concentrated in vacuo. The residue is purified by Xbridge Shield RP18 with a gradient of acetonitrile in 0.1% NH4OH to give an oil. Addition of diethyl ether and a few drops of concentrated HCl, followed by lyophilization affords 1-(4,4-dimethyl-3-oxo-pentyl)-2-pyridin-3-yl-1H-indole-5-carbonitrile as a light yellow color solid. 1H NMR (400 MHz, MeOD) δ ppm (HCl salt) 0.90 (s, 9H), 2.94 (t, J=6.4 Hz, 2H), 4.61 (t, J=6.6 Hz, 2H), 6.88 (s, 1H), 7.59 (dd, J=8.7, 1.6 Hz, 1H), 7.77 (d, J=8.6 Hz, 1H), 7.93 (dd, J=8.0, 5.4 Hz, 1H), 8.10 (d, J=1.0 Hz, 1H), 8.44 (dt, J=7.9, 1.7 Hz, 1H), 8.82 (dd, J=5.3, 1.3 Hz, 1H), 8.96 (d, J=1.8 Hz, 1H). HRMS (ESI) m/z 332.1762 [(M+H)+ Calcd for C21H22N3O: 332.1763].

Workup

  1. stirringthe mixture is stirred at 50° C. overnight
  2. washis washed with water twice
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by Xbridge Shield RP18 with a gradient of acetonitrile in 0.1% NH4OH
  6. customto give an oil

Sources & evidence

ORD record
ord-266e7174c4304e208716a93109aba6c2
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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