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

HRID 2383318Notes

Reaction equation

HRID 2383318 reaction equation
[CH2:1]([O:3][C:4](=[O:30])[CH2:5][CH2:6][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])[CH3:2].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]>CN(C)C=O>[C:38]([C:40]1[CH:41]=[C:42]([C:43]2[O:21][N:20]=[C:18]([C:14]3[C:13]([CH3:22])=[C:12]4[C:17](=[CH:16][CH:15]=3)[CH:8]([CH2:7][CH2:6][CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:30])[N:9]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:10][CH2:11]4)[N:19]=2)[CH:46]=[CH:47][C:48]=1[O:49][CH:50]([CH3:51])[CH3:52])#[N:39]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 575058423-Cyano-4-isopropoxybenzoyl chlorideHCID 178471206HCID 178471206, compound

Product 1

HCID 595910951,1-Dimethylethyl 6-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-[4-(ethyloxy)-4-oxobutyl]-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylateYield 35.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 1,1-dimethylethyl 1-[4-(ethyloxy)-4-oxobutyl]-6-[(hydroxyamino)(imino)methyl]-5-methyl-3,4-dihydro-2(1H)-isoquinolinecarboxylate (Preparation 27; 240 mg, 0.572 mmol) in N,N-dimethylformamide (DMF) (4 ml) was added triethylamine (0.119 ml, 0.858 mmol) followed by 3-cyano-4-[(1-methylethyl)oxy]benzoyl chloride (WO 2008128951; 141 mg, 0.629 mmol) in DMF (2 ml) dropwise over one minute at room temperature under nitrogen. The resulting mixture was stirred for 1 h at room temperature, then warmed up to 120° C. After 2 h at 120° C., most of the solvent was removed, and the residue diluted with ethyl acetate. The solution was washed with sodium bicarbonate then brine, dried over MgSO4 and concentrated in vacuo to give the crude product (ca. 300 mg). Purification by flash chromatography on silica gel, eluting with 8-38% ethyl acetate in cyclohexane, gave the title compound (120 mg) as a white foam.

Workup

  1. temperaturewarmed up to 120° C
  2. waitAfter 2 h at 120° C.
  3. custommost of the solvent was removed
  4. additionthe residue diluted with ethyl acetate
  5. washThe solution was washed with sodium bicarbonate
  6. dry with materialbrine, dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customto give the crude product (ca. 300 mg)
  9. customPurification by flash chromatography on silica gel
  10. washeluting with 8-38% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-57dd31b76a4b41a5af2803d9eb0ef90e
Source dataset
uspto-grants-2012_09
Patent number
US08263620B2

Reaction notes

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