Hydrochloric Acid → 6-[5-(5-chloro-6-isopropoxy-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-1H-indole-3-carbaldehyde

HRID 1512805Notes

Reaction equation

HRID 1512805 reaction equation
[C:1](Cl)(C(Cl)=O)=[O:2].[Cl:7][C:8]1[CH:9]=[C:10]([C:18]2[O:22][N:21]=[C:20]([C:23]3[CH:31]=[C:30]4[C:26]([CH:27]=[CH:28][NH:29]4)=[CH:25][CH:24]=3)[N:19]=2)[CH:11]=[N:12][C:13]=1[O:14][CH:15]([CH3:17])[CH3:16].Cl.[OH-].[Na+]>C(Cl)Cl.O.CN(C=O)C>[Cl:7][C:8]1[CH:9]=[C:10]([C:18]2[O:22][N:21]=[C:20]([C:23]3[CH:31]=[C:30]4[C:26]([C:27]([CH:1]=[O:2])=[CH:28][NH:29]4)=[CH:25][CH:24]=3)[N:19]=2)[CH:11]=[N:12][C:13]=1[O:14][CH:15]([CH3:17])[CH3:16]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 65578Oxalyl chlorideHCID 591460766-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indole

Product 1

HCID 591461746-[5-(5-chloro-6-isopropoxy-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-1H-indole-3-carbaldehyde

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

DMF (0.28 mL) was added dropwise to a solution of (COCl)2 (0.31 mL) in DCM (9 mL) at 0° C. The resulting mixture was stirred at 0° C. for 1 hour. Then a solution of 6-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1H-indole (D101) (1.06 g) in DCM (30 mL) was added. The reaction mixture was warmed to RT and stirred overnight. Then water and 2 M HCl was added. After stirred for 2 hours, the mixture was neutralized with 2 M aqueous NaOH solution until pH was between 8 and 9. The organic layer was separated and washed with brine, dried over anhydrous sodium sulfate. The dried solution was concentrated. The residue was purified by column chromatography to afford 6-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-1H-indole-3-carbaldehyde (D102) (620 mg) as a yellow solid. δH (DMSO-d6, 400 MHz): 1.46 (6H, d), 5.51 (1H, m), 7.99 (1H, d), 8.14 (1H, d), 8.30 (1H, s), 8.42 (1H, d), 8.46 (1H, d), 8.90 (1H, d), 8.98 (1H, br s), 10.12 (1H, d).

Workup

  1. temperatureThe reaction mixture was warmed to RT
  2. stirringstirred overnight
  3. stirringAfter stirred for 2 hours
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationThe dried solution was concentrated
  8. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-50811fdbfcb3487ca7d9e6f747011697
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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