1,1'-Carbonyldiimidazole → 6-{4-[4-(5-chloro-1H-indole-2-sulphonyl)-piperazine-1-carbonyl]-phenyl}-2-methyl-2H-pyridazin-3-one

HRID 28395Notes

Reaction equation

HRID 28395 reaction equation
[CH3:1][N:2]1[C:7](=[O:8])[CH:6]=[CH:5][C:4]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][CH:10]=2)=[N:3]1.C(N1C=CN=C1)(N1C=CN=C1)=O.[Cl:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[NH:36][C:35]([S:40]([N:43]1[CH2:48][CH2:47][NH:46][CH2:45][CH2:44]1)(=[O:42])=[O:41])=[CH:34]2>CN(C)C=O>[Cl:30][C:31]1[CH:32]=[C:33]2[C:37](=[CH:38][CH:39]=1)[NH:36][C:35]([S:40]([N:43]1[CH2:48][CH2:47][N:46]([C:13]([C:12]3[CH:11]=[CH:10][C:9]([C:4]4[CH:5]=[CH:6][C:7](=[O:8])[N:2]([CH3:1])[N:3]=4)=[CH:17][CH:16]=3)=[O:15])[CH2:45][CH2:44]1)(=[O:42])=[O:41])=[CH:34]2

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 227105715-chloro-2-(piperazine-1-sulfonyl)-1H-indoleHCID 671044874-(1-Methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzoic acid

Product 1

HCID 111565156-{4-[4-(5-chloro-1H-indole-2-sulphonyl)-piperazine-1-carbonyl]-phenyl}-2-methyl-2H-pyridazin-3-oneYield 74.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

To a solution of 4-(1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzoic acid, (0.637 g, 2.76 mmol) in N,N-dimethylformamide was added 1,1′-carbonyldiimidazole (0.930 g, 5.74 mmol, 2.07 eq.). The resulting solution was stirred at room temperature for 5 hours, whereupon 5-chloro-2-(piperazin-1-ylsulphonyl)-1H-indole (see WO 99/57113, 0.622 g, 2.08 mmol, 1.11 eq.) was added. The reaction mixture was stirred at 25° C. for 14 h and then evaporated in vacuo. The residue was purified by flash column chromatography: first eluting with ethyl acetate:toluene (2:1), then with ethyl acetate. During concentration of the desired fraction, a white solid precipitated. The solid was triturated with hot ethyl acetate (50 mL) to remove a trace of impurity. After drying, pale yellow solid were isolated. De-colorization on charcoal using hot methanol together with the re-crystallization in methanol, gave 0.79 gram 6-{4-[4-(5-chloro-1H-indole-2-sulphonyl)-piperazine-1-carbonyl]-phenyl}-2-methyl-2H-pyridazin-3-one as fine white crystals (yield 56%).

Workup

  1. additionwas added
  2. customevaporated in vacuo
  3. customThe residue was purified by flash column chromatography
  4. washfirst eluting with ethyl acetate:toluene (2:1)
  5. customDuring concentration of the desired fraction, a white solid precipitated
  6. customThe solid was triturated with hot ethyl acetate (50 mL)
  7. customto remove a trace of impurity
  8. customAfter drying
  9. custompale yellow solid were isolated
  10. customDe-colorization on charcoal using hot methanol together with the re-crystallization in methanol

Sources & evidence

ORD record
ord-be13f1e9db6b4cec9f5270e8f0d8b8da
Source dataset
uspto-grants-2008_09
Patent number
US07419979B2

Reaction notes

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