Imidazole → 2-(4-(Isoxazol-5-yl)benzyl)-7-(4-chlorophenyl)-8-(1H-imidazol-1-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

HRID 2224287Notes

Reaction equation

HRID 2224287 reaction equation
[O:1]1[C:5]([C:6]2[CH:30]=[CH:29][C:9]([CH2:10][N:11]3[C:27](=[O:28])[N:14]4[N:15]=[CH:16][C:17]([C:20]5[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=5)=[C:18](Cl)[C:13]4=[N:12]3)=[CH:8][CH:7]=2)=[CH:4][CH:3]=[N:2]1.[NH:31]1[CH:35]=[CH:34][N:33]=[CH:32]1>CN1CCCC1=O>[O:1]1[C:5]([C:6]2[CH:7]=[CH:8][C:9]([CH2:10][N:11]3[C:27](=[O:28])[N:14]4[N:15]=[CH:16][C:17]([C:20]5[CH:21]=[CH:22][C:23]([Cl:26])=[CH:24][CH:25]=5)=[C:18]([N:31]5[CH:35]=[CH:34][N:33]=[CH:32]5)[C:13]4=[N:12]3)=[CH:29][CH:30]=2)=[CH:4][CH:3]=[N:2]1

Participants

4

Reactant 2

HCID 795ImidazoleHCID 597165402-(4-(isoxazol-5-yl)benzyl)-8-chloro-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

Product 1

HCID 597166232-(4-(Isoxazol-5-yl)benzyl)-7-(4-chlorophenyl)-8-(1H-imidazol-1-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-oneYield 55%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A solution of 2-(4-(isoxazol-5-yl)benzyl)-8-chloro-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (149 mg, 0.34 mmol) and imidazole (69.5 mg, 1.02 mmol) in dry 1-methyl-2-pyrrolidinone (3 mL) was heated at 100° C. for 18 h. HPLC/MS analysis indicated 90% complete reaction. The reaction mixture was concentrated under vacuum with co-evaporation of toluene (5 mL×2) to obtain a dark yellow solid. The crude product was purified by silica gel column chromatography (ISCO) eluting with CH2Cl2/EtOAc to obtain pure title compound (87 mg, 55%) as a yellow solid. MS [M+H]+ 470; HPLC retention time=2.59 min; 1HNMR (400 MHz, CDCl3) δ 8.29 (d, 1H, J=0.5 Hz), 8.18 (s, 1H), 7.80-7.85 (m, 2H), 7.78 (s, 1H), 7.49 (d, 2H, J=7.0 Hz), 7.43 (d, 2H, J=7.0 Hz), 7.13-7.15 (m, 3H), 6.94 (m, 1H), 6.53 (d, 1H, J=0.5 Hz), 5.27 (s, 2H).

Workup

  1. custom90% complete reaction
  2. concentrationThe reaction mixture was concentrated under vacuum with co-evaporation of toluene (5 mL×2)
  3. customto obtain a dark yellow solid
  4. customThe crude product was purified by silica gel column chromatography (ISCO)
  5. washeluting with CH2Cl2/EtOAc

Sources & evidence

ORD record
ord-40e348f2831d44209f67e56bffb1694f
Source dataset
uspto-grants-2008_05
Patent number
US07378418B2

Reaction notes

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