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

HRID 2192503Notes

Reaction equation

HRID 2192503 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH2:12][C:13]([F:16])([F:15])[F:14])[C:5](Cl)=[O:6].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>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:6][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:8]=[CH:9][C:10]=1[O:11][CH2:12][C:13]([F:16])([F:15])[F:14]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 581498703-Chloro-4-[(2,2,2-trifluoroethyl)oxy]benzoyl chlorideHCID 178450938HCID 178450938, compound

Product 1

HCID 581499241,1-Dimethylethyl 3-[5-(5-{3-chloro-4-[(2,2,2-trifluoroethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-isoquinolinyl]propanoateYield 90.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A solution of 3-chloro-4-[(2,2,2-trifluoroethyl)oxy]benzoyl chloride (D21; 82 mg, 0.30 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 then 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 (130 mg). 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 (55 mg).

Workup

  1. stirringat 100° with stirring under nitrogen for 16 h
  2. customThe cooled mixture was partitioned between saturated aqueous sodium bicarbonate (30 ml) and ethyl acetate (3×20 ml)
  3. washthe organic layer was washed with 50:50 brine
  4. dry with materialwater and brine, dried (MgSO4)
  5. customevaporated in vacuo

Sources & evidence

ORD record
ord-ff231a829ecb48479e54d79b787a437c
Source dataset
uspto-grants-2012_12
Patent number
US08329730B2

Reaction notes

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