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

HRID 2059926Notes

Reaction equation

HRID 2059926 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][C:30]([O:32][CH2:33][CH3:34])=[O:31].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[CH:30]([OH:32])=[O:31].[CH2:33]([O:32][C:30](=[O:31])[CH2:29][N:22]1[CH2:21][CH2:20][C:19]2[C:24](=[CH:25][CH:26]=[CH:27][C:18]=2[C:15]2[N:14]=[C:13]([C:10]3[CH:11]=[CH:12][C:5]([O:4][CH:2]([CH3:1])[CH3:3])=[C:6]([C:7]#[N:8])[CH:9]=3)[O:17][N:16]=2)[CH2:23]1)[CH3:34]

Participants

5

Reactant 3

HCID 7748Ethyl bromoacetateHCID 10796Cesium carbonateHCID 441248992-[(1-Methylethyl)oxy]-5-[3-(1,2,3,4-tetrahydro-5-isoquinolinyl)-1,2,4-oxadiazol-5-yl]benzonitrile

Product 1

HCID 131729974Ethyl[5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinolinyl]acetate formic acid

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 bromoacetate (35.5 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. The suspension was added to an SCX cartridge, and the product eluted with methanolic ammonia. Concentration in vacuo gave a crude product (43 mg) that was purified by MDAP to give the title compound as a clear film (11.6 mg, 32%). 1H NMR (400 MHz, CDCl3) δ 8.41 (1H, d), 8.33 (1H, dd), 8.09 (1H, br. s), 8.01 (1H, d), 7.34 (1H, apparent t), 7.21 (1H, d), 7.12 (1H, d), 4.80 (1H, sept), 4.24 (2H, q), 4.00 (2H, s), 3.52 (2H, s), 3.35 (2H, t), 3.07 (2H, t), 1.48 (6H, d), 1.31 (3H, t); m/z (ES) 447 [M+H]+.

Workup

  1. customirradiated to 60° C. for 5 min in the microwave
  2. additionThe suspension was added to an SCX cartridge
  3. washthe product eluted with methanolic ammonia
  4. concentrationConcentration in vacuo
  5. customgave a crude product (43 mg) that
  6. customwas purified by MDAP

Sources & evidence

ORD record
ord-f5646bcb51044bdd9cbbbd4be5649cc0
Source dataset
uspto-grants-2012_10
Patent number
US08278324B2

Reaction notes

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