Dimethylformamide → 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indole-3-carbaldehyde

HRID 1512771Notes

Reaction equation

HRID 1512771 reaction equation
C(Cl)(=O)[C:2](Cl)=[O:3].CN(C)C=O.[Cl:12][C:13]1[CH:14]=[C:15]([C:23]2[O:27][N:26]=[C:25]([C:28]3[CH:29]=[CH:30][CH:31]=[C:32]4[C:36]=3[N:35]([CH3:37])[CH:34]=[CH:33]4)[N:24]=2)[CH:16]=[CH:17][C:18]=1[O:19][CH:20]([CH3:22])[CH3:21]>ClCCl>[Cl:12][C:13]1[CH:14]=[C:15]([C:23]2[O:27][N:26]=[C:25]([C:28]3[CH:29]=[CH:30][CH:31]=[C:32]4[C:36]=3[N:35]([CH3:37])[CH:34]=[C:33]4[CH:2]=[O:3])[N:24]=2)[CH:16]=[CH:17][C:18]=1[O:19][CH:20]([CH3:21])[CH3:22]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 591461677-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indole

Product 1

HCID 591461277-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indole-3-carbaldehyde

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of oxalyl chloride (2.1 mL) in dichloromethane (125 mL) at 0° C. was added a solution of N,N-dimethylformamide (2.32 mL) in Dichloromethane (DCM) (75 mL) dropwise during 30 mins. The reaction mixture was stirred at 0° C. for another 15 minutes. A solution of 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indole (D58) (7.4 g) in Dichloromethane (100 mL) was added in one portion. the mixture was stirred and warmed to room temperature slowly. After stirred at room temperature for 5 hours, dichloromethane was evaporated off. Ethyl acetate (300 mL), water (100 mL) and concentrated HCl solution (5 mL) was added to the residue. The mixture was stirred for 30 minutes and KOH was added to adjust pH value to about 8. The organic layer was separated, washed with water and brine, then dried over MgSO4. Filtration and evaporation afforded the product 7-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1-methyl-1H-indole-3-carbaldehyde (D61) (5.2 g). δH (CDCl3, 400 MHz): 1.47 (6H, d), 3.87 (3H, s), 4.71-4.77 (1H, m), 7.09 (1H, d), 7.44 (1H, t), 7.68 (1H, dd), 7.72 (1H, s), 7.89 (1H, dd), 8.26 (1H, d), 8.56 (1H, dd), 10.06 (1H, s). MS (ES): C21H18ClN3O3 requires 395. found 396.1 (M+H+).

Workup

  1. stirringthe mixture was stirred
  2. temperaturewarmed to room temperature slowly
  3. stirringAfter stirred at room temperature for 5 hours
  4. customdichloromethane was evaporated off
  5. additionEthyl acetate (300 mL), water (100 mL) and concentrated HCl solution (5 mL) was added to the residue
  6. stirringThe mixture was stirred for 30 minutes
  7. additionKOH was added
  8. customThe organic layer was separated
  9. washwashed with water and brine
  10. dry with materialdried over MgSO4
  11. filtrationFiltration and evaporation

Sources & evidence

ORD record
ord-30f6f9591f9e4af99e7b5e79e5052ce7
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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