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

HRID 2192501Notes

Reaction equation

HRID 2192501 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH2:12][CH:13]1[CH2:15][CH2:14]1)[C:5](Cl)=[O:6].O[NH:17][C:18](=[NH:38])[C:19]1[CH:28]=[CH:27][CH:26]=[C:25]2[C:20]=1[CH:21]=[CH:22][N:23]=[C:24]2[CH2:29][CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32].C(N(CC)CC)C>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:6][N:17]=[C:18]([C:19]3[CH:28]=[CH:27][CH:26]=[C:25]4[C:20]=3[CH:21]=[CH:22][N:23]=[C:24]4[CH2:29][CH2:30][C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[N:38]=2)[CH:8]=[CH:9][C:10]=1[O:11][CH2:12][CH:13]1[CH2:15][CH2:14]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 581498783-Chloro-4-[(cyclopropylmethyl)oxy]benzoyl chlorideHCID 178450938HCID 178450938, compound

Product 1

HCID 581499031,1-Dimethylethyl 3-[5-(5-{3-chloro-4-[(cyclopropylmethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-isoquinolinyl]propanoateYield 16.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 3-chloro-4-[(cyclopropylmethyl)oxy]benzoyl chloride (D16; 73.5 mg, 0.3 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; 85 mg, 0.270 mmol) and triethylamine (0.063 ml, 0.450 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 (30 ml) and ethyl acetate (3×20 ml), and the organic layer was washed with 50:50 brine:water and brine, dried (MgSO4) and evaporated in vacuo to give a brown oil. The crude product was purified by flash chromatography on silica gel, eluting with 0-30% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white solid (22 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 (30 ml) and ethyl acetate (3×20 ml)
  4. washthe organic layer was washed with 50:50 brine
  5. dry with materialwater and brine, dried (MgSO4)
  6. customevaporated in vacuo
  7. customto give a brown oil
  8. customThe crude product was purified by flash chromatography on silica gel
  9. washeluting with 0-30% ethyl acetate-cyclohexane
  10. customevaporated in vacuo

Sources & evidence

ORD record
ord-aeec7fbc0c414e8ab5eafb4e727bd3d2
Source dataset
uspto-grants-2012_12
Patent number
US08329730B2

Reaction notes

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