Potassium Carbonate → 2-amino-N,N-dimethyl-5-[8-methyl-4-(4-pyridinyl)-6-quinolinyl]-3-pyridinesulfonamide

HRID 472075Notes

Reaction equation

HRID 472075 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([CH3:12])[CH:11]=1)[N:8]=[CH:7][CH:6]=[C:5]2Cl.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[NH2:37][C:38]1[C:43]([S:44]([N:47]([CH3:49])[CH3:48])(=[O:46])=[O:45])=[CH:42][C:41](Br)=[CH:40][N:39]=1.C(=O)([O-])[O-].[K+].[K+].CC1(C)C(C)(C)OB([C:65]2[CH:70]=[CH:69][N:68]=[CH:67][CH:66]=2)O1>O1CCOCC1.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]>[NH2:37][C:38]1[C:43]([S:44]([N:47]([CH3:49])[CH3:48])(=[O:46])=[O:45])=[CH:42][C:41]([C:2]2[CH:3]=[C:4]3[C:9](=[C:10]([CH3:12])[CH:11]=2)[N:8]=[CH:7][CH:6]=[C:5]3[C:65]2[CH:70]=[CH:69][N:68]=[CH:67][CH:66]=2)=[CH:40][N:39]=1

Participants

9

Reactant 6

HCID 11430Potassium Carbonate2×HCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 27346484-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 435319436-Bromo-4-chloro-8-methylquinolineHCID 523351532-amino-5-bromo-N,N-dimethylpyridine-3-sulfonamide

Product 1

HCID 598600222-amino-N,N-dimethyl-5-[8-methyl-4-(4-pyridinyl)-6-quinolinyl]-3-pyridinesulfonamideYield 28%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst3×HCID 312751,4-DioxaneSolvent2×

Procedure

A mixture of 6-bromo-4-chloro-8-methylquinoline (0.300 g, 1.170 mmol), bis(pinacolato)diboron (0.297 g, 1.170 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.029 g, 0.035 mmol), and solid anhydrous potassium acetate (0.459 g, 4.676 mmol) in dry 1,4-dioxane (8 mL) was heated at reflux for 70 minutes. The oil bath was temporarily removed and to the reaction was added 2-amino-5-bromo-N,N-dimethyl-3-pyridinesulfonamide (0.327 g, 1.17 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.047 g, 0.058 mmol), and 2 M aqueous potassium carbonate (0.646 g, 4.676 mmol, 2.34 mL). The reaction was heated at reflux for 80 minutes. The oil bath was temporarily removed and to the reaction was added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.240 g, 1.17 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) dichloromethane adduct (0.047 g, 0.058 mmol), 2 M aqueous potassium carbonate (0.485 g, 3.51 mmol, 1.76 mL), and 1,4-dioxane (6 mL). The reaction was heated at reflux for 17 h and concentrated in vacuo. The residue was triturated with 10% MeOH:EtOAc (45 mL), filtered through filter paper, and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography on silica gel (7% MeOH:EtOAc) to give the title compound (0.135 g, 28%) as a yellow powder. MS (ES)+ m/e 420 [M+H].

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 70 minutes
  3. customThe oil bath was temporarily removed and to the reaction
  4. temperatureThe reaction was heated
  5. temperatureat reflux for 80 minutes
  6. customThe oil bath was temporarily removed and to the reaction
  7. temperatureThe reaction was heated
  8. temperatureat reflux for 17 h
  9. concentrationconcentrated in vacuo
  10. customThe residue was triturated with 10% MeOH
  11. filtrationEtOAc (45 mL), filtered
  12. filtrationthrough filter paper
  13. concentrationthe filtrate was concentrated in vacuo
  14. customThe residue was purified by flash chromatography on silica gel (7% MeOH:EtOAc)

Sources & evidence

ORD record
ord-04430095f69649339473c41dc7b8b228
Source dataset
uspto-grants-2014_01
Patent number
US08633187B2

Reaction notes

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