Triethylamine → 1,1-Dimethylethyl 1-[2-(butyloxy)-2-oxoethyl]-6-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate

HRID 2383311Notes

Reaction equation

HRID 2383311 reaction equation
[CH2:1]([O:5][C:6](=[O:30])[CH2:7][CH:8]1[C:17]2[C:12](=[C:13]([CH3:22])[C:14]([C:18]([NH:20][OH:21])=[NH:19])=[CH:15][CH:16]=2)[CH2:11][CH2:10][N:9]1[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:2][CH2:3][CH3:4].C(N(CC)CC)C.[C:38]([C:40]1[CH:41]=[C:42]([CH:46]=[CH:47][C:48]=1[O:49][CH:50]([CH3:52])[CH3:51])[C:43](Cl)=O)#[N:39]>O1CCOCC1>[CH2:1]([O:5][C:6](=[O:30])[CH2:7][CH:8]1[C:17]2[C:12](=[C:13]([CH3:22])[C:14]([C:18]3[N:19]=[C:43]([C:42]4[CH:46]=[CH:47][C:48]([O:49][CH:50]([CH3:52])[CH3:51])=[C:40]([C:38]#[N:39])[CH:41]=4)[O:21][N:20]=3)=[CH:15][CH:16]=2)[CH2:11][CH2:10][N:9]1[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:2][CH2:3][CH3:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 575058423-Cyano-4-isopropoxybenzoyl chlorideHCID 178450882HCID 178450882, compound

Product 1

HCID 595910961,1-Dimethylethyl 1-[2-(butyloxy)-2-oxoethyl]-6-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylateYield 11.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 1,1-dimethylethyl 1-[2-(butyloxy)-2-oxoethyl]-6-[(hydroxyamino)(imino)methyl]-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate (Preparation 19; 264 mg, 0.629 mmol) in dioxane (4 ml) was added triethylamine (0.263 ml, 1.89 mmol) followed by dropwise addition of 3-cyano-4-[(1-methylethyl)oxy]benzoyl chloride (preparation described in WO 2008128951; 169 mg, 0.755 mmol) in dioxane (2 ml). The resulting mixture was stirred at room temperature for 90 min, then heated at 100° C. for 24 h. The mixture was cooled to room temperature and most of the solvent removed in vacuo. The residue was partitioned between ethyl acetate and saturated sodium bicarbonate. The layers were separated, and the aqueous layer further extracted with ethyl acetate. The combined organic phases were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification by flash chromatography, eluting with 5-25% ethyl acetate in cyclohexane, gave the title compound as a pale yellow oil (41 mg).

Workup

  1. temperatureheated at 100° C. for 24 h
  2. temperatureThe mixture was cooled to room temperature and most of the solvent
  3. customremoved in vacuo
  4. customThe residue was partitioned between ethyl acetate and saturated sodium bicarbonate
  5. customThe layers were separated
  6. extractionthe aqueous layer further extracted with ethyl acetate
  7. washThe combined organic phases were washed with brine
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated in vacuo
  10. customPurification by flash chromatography
  11. washeluting with 5-25% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-3256da41959e48aca0cd9caeba789ce3
Source dataset
uspto-grants-2012_09
Patent number
US08263620B2

Reaction notes

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