Indole → HCID 46893454, compound

HRID 2381077Notes

Reaction equation

HRID 2381077 reaction equation
[OH-].[K+].[F:3][C:4]([F:22])([F:21])[C:5]1[N:9]2[N:10]=[C:11]([N:14]3[CH2:19][CH2:18][C:17](=O)[CH2:16][CH2:15]3)[CH2:12][CH2:13][C:8]2=[N:7][N:6]=1.[NH:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[CH:25]=[CH:24]1>CO>[NH:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25]([C:17]2[CH2:18][CH2:19][N:14]([C:11]3[CH2:12][CH2:13][C:8]4[N:9]([C:5]([C:4]([F:22])([F:21])[F:3])=[N:6][N:7]=4)[N:10]=3)[CH2:15][CH:16]=2)=[CH:24]1

Participants

5

Reactant 3

HCID 798IndoleHCID 14797Potassium HydroxideHCID 68502134HCID 68502134, compound

Product 1

HCID 46893454HCID 46893454, compoundYield 40%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
65 °C

Procedure

Potassium hydroxide (156 mg, 2.79 mmol) was added to 1-[3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperidin-4-one (200 mg, 0.70 mmol) and 1H-indole (90 mg, 0.77 mmol) in MeOH (3 mL). The resulting mixture was stirred at 65° C. for 20 hours. The reaction mixture was evaporated to dryness then quenched with saturated aqueous ammonium chloride (0.5 mL), diluted with water (50 mL) and extracted with ethyl acetate (2×50 mL). The combined organic layers were washed with saturated brine (25 mL), dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM. Pure fractions were evaporated to dryness to afford 6-[4-(1H-indol-3-yl)-5,6-dihydropyridin-1(2H)-yl]-3-(trifluoromethyl)-7,8-dihydro-[1,2,4]triazolo[4,3-b]pyridazine (107 mg, 40%) as a solid.

Workup

  1. customThe reaction mixture was evaporated to dryness
  2. customthen quenched with saturated aqueous ammonium chloride (0.5 mL)
  3. additiondiluted with water (50 mL)
  4. extractionextracted with ethyl acetate (2×50 mL)
  5. washThe combined organic layers were washed with saturated brine (25 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customto afford crude product
  10. customThe crude product was purified by flash silica chromatography, elution gradient 0 to 5% MeOH in DCM
  11. customPure fractions were evaporated to dryness

Sources & evidence

ORD record
ord-9196cac2617c45039d9e1ea3f7559e17
Source dataset
uspto-grants-2012_09
Patent number
US08258140B2

Reaction notes

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