Ethyl bromoacetate → ethyl[6-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-5-methyl-3,4-dihydro-2(1H)-isoquinolinyl]acetate

HRID 2059942Notes

Reaction equation

HRID 2059942 reaction equation
FC(F)(F)C(O)=O.[CH3:8][CH:9]([O:11][C:12]1[CH:19]=[CH:18][C:17]([C:20]2[O:24][N:23]=[C:22]([C:25]3[C:26]([CH3:35])=[C:27]4[C:32](=[CH:33][CH:34]=3)[CH2:31][NH:30][CH2:29][CH2:28]4)[N:21]=2)=[CH:16][C:13]=1[C:14]#[N:15])[CH3:10].Br[CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C.O>[CH2:41]([O:40][C:38](=[O:39])[CH2:37][N:30]1[CH2:29][CH2:28][C:27]2[C:32](=[CH:33][CH:34]=[C:25]([C:22]3[N:21]=[C:20]([C:17]4[CH:18]=[CH:19][C:12]([O:11][CH:9]([CH3:8])[CH3:10])=[C:13]([C:14]#[N:15])[CH:16]=4)[O:24][N:23]=3)[C:26]=2[CH3:35])[CH2:31]1)[CH3:42]

Participants

6

Reactant 3

HCID 7748Ethyl bromoacetateHCID 10796Cesium carbonateHCID 575058522-[(1-Methylethyl)oxy]-5-[3-(5-methyl-1,2,3,4-tetrahydro-6-isoquinolinyl)-1,2,4-oxadiazol-5-yl]benzonitrile trifluoroacetate

Product 1

HCID 57505854ethyl[6-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-5-methyl-3,4-dihydro-2(1H)-isoquinolinyl]acetateYield 92.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-[(1-methylethyl)oxy]-5-[3-(5-methyl-1,2,3,4-tetrahydro-6-isoquinolinyl)-1,2,4-oxadiazol-5-yl]benzonitrile trifluoroacetic acid salt (Example 11; 100 mg, 0.20 mmol), ethyl bromoacetate (44 mg, 30 μl, 0.26 mmol) and caesium carbonate (200 mg, 0.61 mmol) in dry DMF (3 ml) was stirred at room temperature for 1 hour. The reaction mixture was diluted with water (10 ml) and extracted with ethyl acetate (3×5 ml). The combined extracts were dried and evaporated. Purification by chromatography on silica gel, eluting with 10% ethyl acetate in cyclohexane gave the title compound as a colourless oil (85 mg). MS m/z 461 [MH]+.

Workup

  1. extractionextracted with ethyl acetate (3×5 ml)
  2. customThe combined extracts were dried
  3. customevaporated
  4. customPurification by chromatography on silica gel
  5. washeluting with 10% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-1c9fdc3d2efd4a58978bdec5eaaadcfb
Source dataset
uspto-grants-2012_10
Patent number
US08278324B2

Reaction notes

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