Triethylamine → 1,1-Dimethylethyl 3-[5-(5-{3-cyano-4-[(cyclopropylmethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-isoquinolinyl]propanoate

HRID 2192504Notes

Reaction equation

HRID 2192504 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH2:13][CH:14]1[CH2:16][CH2:15]1)[C:6](Cl)=[O:7])#[N:2].O[NH:18][C:19](=[NH:39])[C:20]1[CH:29]=[CH:28][CH:27]=[C:26]2[C:21]=1[CH:22]=[CH:23][N:24]=[C:25]2[CH2:30][CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33].C(N(CC)CC)C>CN(C=O)C>[C:1]([C:3]1[CH:4]=[C:5]([C:6]2[O:7][N:18]=[C:19]([C:20]3[CH:29]=[CH:28][CH:27]=[C:26]4[C:21]=3[CH:22]=[CH:23][N:24]=[C:25]4[CH2:30][CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[N:39]=2)[CH:9]=[CH:10][C:11]=1[O:12][CH2:13][CH:14]1[CH2:16][CH2:15]1)#[N:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 866511443-Cyano-4-[(cyclopropylmethyl)oxy]benzoyl chlorideHCID 178450938HCID 178450938, compound

Product 1

HCID 668773731,1-Dimethylethyl 3-[5-(5-{3-cyano-4-[(cyclopropylmethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-isoquinolinyl]propanoateYield 33.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 3-cyano-4-[(cyclopropylmethyl)oxy]benzoyl chloride (D25; 54.2 mg, 0.23 mmol) in dry DMF (1.5 ml) was added to a stirred solution of 1,1-dimethylethyl 3-{5-[(hydroxyamino)(imino)methyl]-1-isoquinolinyl}propanoate (D36; 68.9 mg, 0.219 mmol) and triethylamine (0.048 ml, 0.345 mmol) in dry DMF (1.5 ml) at 0° and the mixture was stirred at 0° for 1.5 h. The mixture was then heated at 100° with stirring under nitrogen for 16 h. The cooled mixture was partitioned between saturated aqueous sodium bicarbonate (40 ml) and ethyl acetate (3×25 ml), and the combined organic layers washed with 50:50 brine:water and brine, dried (MgSO4) and evaporated in vacuo to give a brown oil which was purified by flash chromatography on silica gel, eluting with 0-40% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as an off-white solid (36 mg)

Workup

  1. temperatureThe mixture was then heated at 100°
  2. stirringwith stirring under nitrogen for 16 h
  3. customThe cooled mixture was partitioned between saturated aqueous sodium bicarbonate (40 ml) and ethyl acetate (3×25 ml)
  4. washthe combined organic layers washed with 50:50 brine
  5. dry with materialwater and brine, dried (MgSO4)
  6. customevaporated in vacuo
  7. customto give a brown oil which
  8. customwas purified by flash chromatography on silica gel
  9. washeluting with 0-40% ethyl acetate-cyclohexane
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-64363e385fd2465fbd916bc4fc40d2cf
Source dataset
uspto-grants-2012_12
Patent number
US08329730B2

Reaction notes

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