Cesium carbonate → ethyl 3-[5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]-2,2-dimethylpropanoate

HRID 2189793Notes

Reaction equation

HRID 2189793 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[C:19]4[C:23](=[CH:24][CH:25]=3)[NH:22][N:21]=[CH:20]4)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].Br[CH2:27][C:28]([CH3:35])([CH3:34])[C:29]([O:31][CH2:32][CH3:33])=[O:30].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:18]=[C:19]4[C:23](=[CH:24][CH:25]=3)[N:22]([CH2:27][C:28]([CH3:35])([CH3:34])[C:29]([O:31][CH2:32][CH3:33])=[O:30])[N:21]=[CH:20]4)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:25]=[CH:24][C:23]4[C:19](=[CH:20][N:21]([CH2:27][C:28]([CH3:35])([CH3:34])[C:29]([O:31][CH2:32][CH3:33])=[O:30])[N:22]=4)[CH:18]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

6

Reactant 3

HCID 10796Cesium carbonate2×HCID 12373576Ethyl 3-bromo-2,2-dimethylpropanoate2×HCID 532392355-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazole

Product 2

HCID 59316703ethyl 3-[5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2H-indazol-2-yl]-2,2-dimethylpropanoateYield 30%HCID 59316790ethyl 3-[5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]-2,2-dimethylpropanoateYield 55%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazole (D4) (122 mg, 0.344 mmol) in DMF (2 ml) was treated with ethyl 3-bromo-2,2-dimethylpropanoate (D98) (79 mg, 0.378 mmol) and Cs2CO3 (134 mg, 0.413 mmol) and the resulting mixture was stirred at 80° C. overnight. More ethyl 3-bromo-2,2-dimethylpropanoate (D98) (29 mg, 0.4 mmol) and Cs2CO3 (56 mg, 0.5 mmol) were added and the resulting mixture stirred at 80° C. for 6 h then cooled to room temperature and concentrated in vacuo. The residue was dissolved in EtOAc and the organic phase was washed with water then brine, dried and concentrated in vacuo. Purification of the residue by flash chromatography on silica gel [gradient ethyl acetate/cyclohexane] gave ethyl 3-[5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indazol-1-yl]-2,2-dimethylpropanoate (D100) (92 mg, 55%) and ethyl 3-[5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-2H-indazol-2-yl]-2,2-dimethylpropanoate (D101) (49 mg, 30%). MS (ES) C25H27ClN4O4 requires 482, found 483 [M+H]+

Workup

  1. stirringthe resulting mixture stirred at 80° C. for 6 h
  2. temperaturethen cooled to room temperature
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in EtOAc
  5. washthe organic phase was washed with water
  6. dry with materialbrine, dried
  7. concentrationconcentrated in vacuo
  8. customPurification of the residue by flash chromatography on silica gel [gradient ethyl acetate/cyclohexane]

Sources & evidence

ORD record
ord-132d476a3f274967b16d062bfb5d7296
Source dataset
uspto-grants-2012_12
Patent number
US08324254B2

Reaction notes

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