Cesium carbonate → 6-{4-[4-(5-chloro-1H-indole-2-sulphonyl)-piperazine-1-carbonyl]-phenyl}-2-(2-dimethylamino-ethyl)-2H-pyridazin-3-one

HRID 28398Notes

Reaction equation

HRID 28398 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5](=[O:13])[N:6]([CH2:8][CH2:9][N:10]([CH3:12])[CH3:11])[N:7]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][C:25]([S:30]([N:33]1[CH2:38][CH2:37][N:36]([C:39]([C:41]3[CH:46]=[CH:45][C:44](B(O)O)=[CH:43][CH:42]=3)=[O:40])[CH2:35][CH2:34]1)(=[O:32])=[O:31])=[CH:24]2>COCCOC.O.C(O)C.C1(C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)[Pd][P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][CH:29]=1)[NH:26][C:25]([S:30]([N:33]1[CH2:34][CH2:35][N:36]([C:39]([C:41]3[CH:42]=[CH:43][C:44]([C:2]4[CH:3]=[CH:4][C:5](=[O:13])[N:6]([CH2:8][CH2:9][N:10]([CH3:12])[CH3:11])[N:7]=4)=[CH:45][CH:46]=3)=[O:40])[CH2:37][CH2:38]1)(=[O:31])=[O:32])=[CH:24]2

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 693065836-Chloro-2-(2-(dimethylamino)ethyl)pyridazin-3(2H)-oneHCID 693073894-({4-[(5-chloro-1H-indol-2-yl)sulphonyl]piperazin-1-yl}carbonyl)phenyl boronic acid

Product 1

HCID 113765326-{4-[4-(5-chloro-1H-indole-2-sulphonyl)-piperazine-1-carbonyl]-phenyl}-2-(2-dimethylamino-ethyl)-2H-pyridazin-3-oneYield 60.7%

Reagents, catalysts & solvents 2

HCID 178419050HCID 178419050, compoundCatalystHCID 86587095Dimethoxyethane ethanol waterSolvent

Conditions

Temperature
150 °C

Procedure

6-Chloro-2-(2-dimethylamino-ethyl)-2H-pyridazin-3-one (76 mg, 0.38 mmol), cesium carbonate (122 mg, 0.38 mmol) and bis(triphenylphosphine)palladium II chloride (21.9 mg, 0.03 mmol) was added to a microwave vial. The vial was evacuated and filled with argon twice. 4-({4-[(5-Chloro-1H-indol-2-yl)sulphonyl]piperazin-1-yl}carbonyl)phenyl boronic acid (140 mg, 0.31 mmol) dissolved in 4 mL 1,2-di-methoxyethane/water/ethanol (7:3:2) was added and the vial was once again evacuated and filled with argon. The reaction mixture was heated at 150° C. for 100 seconds, filtrated and purified by preparative HPLC using a gradient of acetonitrile/5% acetonitrile-water phase containing 0.1M ammonium acetate, to give 107 mg of 6-{4-[4-(5-chloro-1H-indole-2-sulphonyl)-piperazine-1-carbonyl]-phenyl}-2-(2-dimethylamino-ethyl)-2H-pyridazin-3-one after evaporation and freeze drying over night (60% yield).

Workup

  1. customThe vial was evacuated
  2. additionfilled with argon twice
  3. additionwas added
  4. customthe vial was once again evacuated
  5. additionfilled with argon
  6. filtrationfiltrated
  7. custompurified by preparative HPLC
  8. additioncontaining 0.1M ammonium acetate

Sources & evidence

ORD record
ord-aea1d9dadd1a420a85b7a6d8f88c0541
Source dataset
uspto-grants-2008_09
Patent number
US07419979B2

Reaction notes

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