Sodium Bicarbonate → HCID 178427385, compound

HRID 513857Notes

Reaction equation

HRID 513857 reaction equation
[NH2:1][C:2]1[N:6]([C:7]2[CH:16]=[CH:15][C:10]3[NH:11][C:12]([CH3:14])=[N:13][C:9]=3[CH:8]=2)[N:5]=[CH:4][C:3]=1[C:17]([C:19]1[N:20]([S:29]([C:32]2[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=2)(=[O:31])=[O:30])[C:21]2[C:26]([CH:27]=1)=[CH:25][CH:24]=[C:23](I)[CH:22]=2)=[O:18].C([O-])(=O)C.[K+].Br[C:45]1[CH:50]=[CH:49][N:48]=[N:47][CH:46]=1.C(=O)(O)[O-].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].ClCCl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1.ClCCl.CO.CS(C)=O>[NH2:1][C:2]1[N:6]([C:7]2[CH:16]=[CH:15][C:10]3[NH:11][C:12]([CH3:14])=[N:13][C:9]=3[CH:8]=2)[N:5]=[CH:4][C:3]=1[C:17]([C:19]1[N:20]([S:29]([C:32]2[CH:37]=[CH:36][C:35]([CH3:38])=[CH:34][CH:33]=2)(=[O:31])=[O:30])[C:21]2[C:26]([CH:27]=1)=[CH:25][CH:24]=[C:23]([C:45]1[CH:50]=[CH:49][N:48]=[N:47][CH:46]=1)[CH:22]=2)=[O:18]

Participants

10

Reactant 4

HCID 516892Sodium BicarbonateHCID 517044Potassium AcetateHCID 178889274-BromopyridazineHCID 178427388HCID 178427388, compound

Product 1

HCID 178427385HCID 178427385, compound

Reagents, catalysts & solvents 5

HCID 178418476HCID 178418476, compoundCatalystHCID 178418807HCID 178418807, compoundCatalystHCID 679Dimethyl SulfoxideSolventHCID 312751,4-DioxaneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of [5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-[6-iodo-1-(toluene-4-sulfonyl)-1H-indol-2-yl]-methanone (194.9 mg, 0.306 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloro-palladium (II)/dichloromethane adduct (14.4 mg, 0.015 mmol) bis(pinacol)diborane (100.9 mg, 0.397 mmol), potassium acetate (132.3 mg, 1.35 mmol), and anhydrous dimethylsulfoxide (DMSO) (1.5 ml) was deaerated. Then, the air was replaced three times with argon, and was heated and stirred at 110° C. for six hours. Then, the reaction mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate. The desiccant was removed by filtration, and concentration was performed. Then, the residue obtained by concentration under reduced pressure was subjected to silica gel column chromatography (dichloromethane/methanol=15/1). The resulting crude product was mixed with 4-bromo-pyridazine (78.0 mg, 0.491 mol), dichlorobis(triphenylphosphine)palladium (II) (17.2 mg, 0.025 mmol), an aqueous solution of 2 M sodium bicarbonate (0.325 mmol), and dioxane (0.4 ml). After deaeration, the air was replaced three times with argon, and this was microwaved at 150° C. for five minutes. Then, the reaction mixture was extracted with ethyl acetate. The extract was dried over anhydrous sodium sulfate. The desiccant was removed by filtration, and concentration was performed. Then, the residue obtained by concentration under reduced pressure was purified by silica gel column chromatography (dichloromethane/methanol=1% to 12%). Thus, [5-amino-1-(2-methyl-1H-benzimidazol-5-yl)-1H-pyrazol-4-yl]-[6-pyridazin-4-yl-1-(toluene-4-sulfonyl)-1H-indol-2-yl]-methanone was obtained as a pale yellow amorphous material (20.0 mg, yield of 11%).

Workup

  1. temperaturewas heated
  2. extractionThen, the reaction mixture was extracted with ethyl acetate
  3. dry with materialThe extract was dried over anhydrous sodium sulfate
  4. customThe desiccant was removed by filtration, and concentration
  5. customThen, the residue obtained by concentration under reduced pressure
  6. customthis was microwaved at 150° C. for five minutes
  7. extractionThen, the reaction mixture was extracted with ethyl acetate
  8. dry with materialThe extract was dried over anhydrous sodium sulfate
  9. customThe desiccant was removed by filtration, and concentration
  10. customThen, the residue obtained by concentration under reduced pressure
  11. customwas purified by silica gel column chromatography (dichloromethane/methanol=1% to 12%)

Sources & evidence

ORD record
ord-ad66827e8f4c4f66a86a5966f398e9c8
Source dataset
uspto-grants-2015_08
Patent number
US09102692B2

Reaction notes

Loading…