Triethylamine → HCID 59909808, compound

HRID 1279866Notes

Reaction equation

HRID 1279866 reaction equation
[C:1]([O:5][C:6](=[O:28])[CH2:7][C@H:8]([C:18]1[O:22][N:21]=[C:20]([C:23]([O:25]CC)=O)[N:19]=1)[CH2:9][CH2:10][CH2:11][CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:36][N:37]([CH3:42])[CH:38]1[CH2:41][NH:40][CH2:39]1>C(O)C>[CH:12]1([CH2:11][CH2:10][CH2:9][C@@H:8]([C:18]2[O:22][N:21]=[C:20]([C:23]([N:40]3[CH2:41][CH:38]([N:37]([CH3:42])[CH3:36])[CH2:39]3)=[O:25])[N:19]=2)[CH2:7][C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:28])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 10351656N,N-dimethylazetidin-3-amineHCID 59909797ethyl 5-{(1R)-1-[2-(tert-butoxy)-2-oxoethyl]4-cyclohexylbutyl}-1,2,4-oxadiazole-3-carboxylate

Product 1

HCID 59909808HCID 59909808, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A solution of ethyl 5{(1R)-1-[2-(tert-butoxy)-2-oxoethyl]4-cyclohexylbutyl}-1,2,4-oxadiazole-3-carboxylate (Preparation 3) (360 mg, 0.91 mmol) and triethylamine (370 mg, 3.65 mmol) in ethanol (5 ml) was treated with N,N-dimethyl-3-azetidinamine (J.Med.Chem.;36; 801; 1993) (300 mg, 0.91 mmol) and the resulting mixture was heated at 80° C. under a nitrogen atmosphere for 16 hours. The mixture was partitioned between ethyl acetate (150 ml) and saturated aqueous ammonium chloride solution (150 ml). The organic layer was washed with saturated ammonium chloride solution (150 ml), water (150 ml) and brine (150 ml), dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient system of pentane:ethyl acetate:diethylamine (87.5:12.5:0.25) gradually changing to pentane:ethyl acetate: diethylamine (50:50:1) to afford the title compound as a colourless oil (355 mg).

Workup

  1. customThe mixture was partitioned between ethyl acetate (150 ml) and saturated aqueous ammonium chloride solution (150 ml)
  2. washThe organic layer was washed with saturated ammonium chloride solution (150 ml), water (150 ml) and brine (150 ml)
  3. dry with materialdried over anhydrous sodium sulphate
  4. filtrationfiltered
  5. customthe solvent removed under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel eluting with a gradient system of pentane:ethyl acetate:diethylamine (87.5:12.5:0.25)

Sources & evidence

ORD record
ord-b72cd6602d9e4d1a97d84bc726954209
Source dataset
uspto-grants-2002_09
Patent number
US06448278B2

Reaction notes

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