Potassium Carbonate → Ethyl 3-[5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]propanoate

HRID 423295Notes

Reaction equation

HRID 423295 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][CH:21]=[CH:20]4)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].C([O-])([O-])=O.[K+].[K+].Br[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36]>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]([CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH:21]=[CH:20]4)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 68320Ethyl 3-bromopropionate2×HCID 593183535-(3-Chloro-4-isopropoxyphenyl)-3-(1H-indol-5-yl)-1,2,4-oxadiazole

Product 1

HCID 59318382Ethyl 3-[5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indol-1-yl]propanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

D5 (100 mg) was dissolved in DMF (1.5 ml). To this solution was added K2CO3 (58 mg) followed by ethyl 3-bromopropionate (72 ul) and the mixture stirred and heated to 100° C. After 1 hour only 5% conversion was observed by LCMS so further portions of K2CO3 (97 mg) and ethyl 3-bromopropionate (72 ul) were added. After 3 hours the reaction mixture was evaporated then partitioned between DCM and H2O. The aqueous layer was extracted with DCM then the combined DCM solutions were washed with brine, dried over MgSO4, filtered and evaporated to give the crude product. This was purified on a silica cartridge, eluting with a 0 to 50% mixture of Et2O in petroleum ether. This gave the title compound (40 mg) as a white solid. δH (CDCl3, 400 MHz): 1.21 (3H, t), 1.45 (6H, d), 2.85 (2H, t), 4.13 (2H, q), 4.51 (2H, t), 4.71 (1H, septet), 6.60 (1H, d), 7.07 (1H, d), 7.21 (1H, d), 7.45 (1H, d), 8.02 (1H, d), 8.08 (1H, d), 8.27 (1H, s), 8.47 (1H, s). MS (ES): C24H24ClN3O4 requires 453; found 454 (MH+).

Workup

  1. additionwere added
  2. customAfter 3 hours the reaction mixture was evaporated
  3. customthen partitioned between DCM and H2O
  4. extractionThe aqueous layer was extracted with DCM
  5. washthe combined DCM solutions were washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto give the crude product
  10. customThis was purified on a silica cartridge
  11. washeluting with a 0 to 50% mixture of Et2O in petroleum ether

Sources & evidence

ORD record
ord-46d8bf1a4ad4482183b6f21fab016ea2
Source dataset
uspto-grants-2012_01
Patent number
US08101775B2

Reaction notes

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