Dichloromethane → 3-(4-Morpholinylsulfonyl)-5-[4-(4-pyridinyl)-6-quinolinyl]-2-pyridinamine

HRID 1625966Notes

Reaction equation

HRID 1625966 reaction equation
Br[C:2]1[CH:3]=[C:4]([S:9]([N:12]2[CH2:17][CH2:16][O:15][CH2:14][CH2:13]2)(=[O:11])=[O:10])[C:5]([NH2:8])=[N:6][CH:7]=1.[N:18]1[CH:23]=[CH:22][C:21]([C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[C:31](B4OC(C)(C)C(C)(C)O4)[CH:32]=3)[N:27]=[CH:26][CH:25]=2)=[CH:20][CH:19]=1.ClCCl.C([O-])([O-])=O.[K+].[K+]>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].O1CCOCC1>[N:12]1([S:9]([C:4]2[C:5]([NH2:8])=[N:6][CH:7]=[C:2]([C:31]3[CH:32]=[C:33]4[C:28](=[CH:29][CH:30]=3)[N:27]=[CH:26][CH:25]=[C:24]4[C:21]3[CH:22]=[CH:23][N:18]=[CH:19][CH:20]=3)[CH:3]=2)(=[O:11])=[O:10])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 621482705-Bromo-3-(morpholinosulfonyl)pyridin-2-amineHCID 667823744-(4-Pyridinyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline

Product 1

HCID 251212683-(4-Morpholinylsulfonyl)-5-[4-(4-pyridinyl)-6-quinolinyl]-2-pyridinamineYield 37%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of 5-bromo-3-(4-morpholinylsulfonyl)-2-pyridinamine (0.296 g, 0.92 mmol), 4-(4-pyridinyl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)quinoline (0.306 mg, 0.92 mmol), [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II)-complex with dichloromethane (1:1) (37.6 mg, 0.046 mmol), 2 M aqueous K2CO3 (5 mL) and dioxane (5 mL) was heated at 100° C. for 18 h. After cooling to room temperature, the organic layer was separated and the aqueous portion extracted three times with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified twice by silica gel chromatography (eluent: i) 1-5% MeOH in CH2Cl2 and ii) 0-20% MeOH in CH2Cl2) to provide the title compound as a white solid (150 mg, 37% yield). MS(ES)+ m/e 448.0 [M+H]+.

Workup

  1. temperatureAfter cooling to room temperature
  2. customthe organic layer was separated
  3. extractionthe aqueous portion extracted three times with EtOAc
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified twice by silica gel chromatography (eluent: i) 1-5% MeOH in CH2Cl2 and ii) 0-20% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-40e3b2a07cbb4be9a21535c07f82bdaf
Source dataset
uspto-grants-2014_07
Patent number
US08785433B2

Reaction notes

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