Cesium carbonate → ethyl 4-[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinolinyl]butanoate formic acid salt

HRID 2059928Notes

Reaction equation

HRID 2059928 reaction equation
[CH3:1][CH:2]([O:4][C:5]1[CH:12]=[CH:11][C:10]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:27]=[CH:26][CH:25]=[C:24]4[C:19]=3[CH2:20][CH2:21][NH:22][CH2:23]4)[N:14]=2)=[CH:9][C:6]=1[C:7]#[N:8])[CH3:3].Br[CH2:29][CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH:32]([OH:34])=[O:33].[C:7]([C:6]1[CH:9]=[C:10]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:27]=[CH:26][CH:25]=[C:24]4[C:19]=3[CH2:20][CH2:21][N:22]([CH2:29][CH2:30][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:23]4)[N:14]=2)[CH:11]=[CH:12][C:5]=1[O:4][CH:2]([CH3:1])[CH3:3])#[N:8]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 76300Ethyl 4-bromobutyrate2×HCID 441248992-[(1-Methylethyl)oxy]-5-[3-(1,2,3,4-tetrahydro-5-isoquinolinyl)-1,2,4-oxadiazol-5-yl]benzonitrile

Product 1

HCID 68500834ethyl 4-[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinolinyl]butanoate formic acid salt

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A suspension of 2-[(1-methylethyl)oxy]-5-[3-(1,2,3,4-tetrahydro-5-isoquinolinyl)-1,2,4-oxadiazol-5-yl]benzonitrile (Example 3, 28.8 mg, 0.080 mmol), ethyl 4-bromobutyrate (45.8 μl, 0.32 mmol) and Cs2CO3 (130 mg, 0.40 mmol) in DMF (2 mL) was stirred at room temperature for 1 h, and then irradiated to 60° C. for 5 min in the microwave. More ethyl 4-bromobutyrate (45.8 μl, 0.32 mmol) was added and the suspension was stirred at room temperature for 3.5 h. It was then filtered, concentrated in vacuo and purified by MDAP to give the title compound as a yellow film (8.0 mg, 21%). 1H NMR (400 MHz, CDCl3) δ 8.42 (1H, d), 8.34 (1H, dd), 8.27 (br. s), 8.09 (1H, d), 7.39 (1H, t), 7.27 (1H, d), 7.13 (1H, d), 4.80 (1H, sept), 4.19 (2H, s), 4.13 (2H, q), 3.47 (2H, t), 3.28 (2H, t), 2.99 (2H, t), 2.44 (2H, t), 2.10 (2H, quin), 1.48 (6H, d), 1.25 (3H, t); m/z (ES) 475 [M+H]+.

Workup

  1. customirradiated to 60° C. for 5 min in the microwave
  2. stirringthe suspension was stirred at room temperature for 3.5 h
  3. filtrationIt was then filtered
  4. concentrationconcentrated in vacuo
  5. custompurified by MDAP

Sources & evidence

ORD record
ord-165c1bfa5eee4175b170599625078d91
Source dataset
uspto-grants-2012_10
Patent number
US08278324B2

Reaction notes

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