Potassium Carbonate → (R)-7,8-Bis(4-chlorophenyl)-2-(2-hydroxyhexyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

HRID 2224227Notes

Reaction equation

HRID 2224227 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]3[C:14](=[O:17])[NH:15][N:16]=[C:10]3[C:9]=2[C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.[O:25]1[C@H:27]([CH2:28][CH2:29][CH2:30][CH3:31])[CH2:26]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]3[C:14](=[O:17])[N:15]([CH2:26][C@H:27]([OH:25])[CH2:28][CH2:29][CH2:30][CH3:31])[N:16]=[C:10]3[C:9]=2[C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 1560627(2R)-2-ButyloxiraneHCID 111641617,8-bis(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

Product 1

HCID 69198036(R)-7,8-Bis(4-chlorophenyl)-2-(2-hydroxyhexyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-oneYield 32.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To a solution of 7,8-bis(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one, (20 mg, 0.056 mmol), prepared as described in Example 1, in 0.6 mL of DMF was added (R)-(+)-1,2-epoxyhexane (5.6 mg, 0.056 mmol), followed by K2CO3 (15.5 mg, 0.112 mmol). The mixture was heated at 85° C. After stirring overnight, the reaction was allowed to cool to RT The reaction mixture was filtered to remove excess of K2CO3. The collected solution was concentrated under reduced pressure. The crude product was purified using silica gel column chromatography using an automated system, eluting with a gradient of (0% to 60% EtOAc/hexanes for 30 min followed by 60% EtOAc/hexanes to 100% EtOAc for 10 min. The title compound, (R)-7,8-Bis(4-chlorophenyl)-2-(2-hydroxyhexyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (8.3 mg, 32% yield) was obtained as a yellow oil. MS [M+H]+: found 457; 1H NMR (CDCl3, 400 MHz) δ 8.12 (s, 1H), 7.28-7.19 (m, 6H), 7.06-7.02 (m, 2H), 4.13-4.08 (m, 1H), 4.00-3.90 (m, 2H), 1.49-1.24 (m, 6H), 0.83 (t, 3H).

Workup

  1. temperatureto cool to RT The reaction mixture
  2. filtrationwas filtered
  3. customto remove excess of K2CO3
  4. concentrationThe collected solution was concentrated under reduced pressure
  5. customThe crude product was purified
  6. washeluting with a gradient of (0% to 60% EtOAc/hexanes for 30 min
  7. waitfollowed by 60% EtOAc/hexanes to 100% EtOAc for 10 min

Sources & evidence

ORD record
ord-9ce6339dfc31442eb0e7368b002059b8
Source dataset
uspto-grants-2008_05
Patent number
US07378418B2

Reaction notes

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