Water → HCID 86636773, compound

HRID 2069787Notes

Reaction equation

HRID 2069787 reaction equation
BrC1C(C(C)(C)O[SiH2]C(C)(C)C)=C(N2C=[CH:16][C:15]3[C:10](=[CH:11][C:12]([C:18]4([CH3:21])[CH2:20][CH2:19]4)=[CH:13][CH:14]=3)[C:9]2=O)C=CC=1.[CH3:32][N:33]1C=C(B2OC(C)(C)C(C)(C)O2)C=C(NC2C=CC(C(N3CCOCC3)=O)=CN=2)C1=O.O.C(=O)([O-])[O-:66].[Cs+].[Cs+]>O1CCOCC1.ClCCl.CO>[CH3:21][C:18]1([C:12]2[CH:11]=[C:10]3[C:15](=[CH:14][CH:13]=2)[C:16](=[O:66])[NH:33][CH:32]=[CH:9]3)[CH2:19][CH2:20]1

Participants

8

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 592164661-Methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-oneHCID 178455416HCID 178455416, compound

Product 1

HCID 86636773HCID 86636773, compoundYield 63.4%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
135 °C

Procedure

2-[3-Bromo-2-(tert-butyl-dimethyl-silanyloxymethyl)-phenyl]-7-(1-methyl-cyclopropyl)-2H-isoquinolin-1-one (0.102 g, 0.205 mmol) and 1-Methyl-3-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyridin-2-one (0.1 g, 0.227 mmol) were dissolved in 2.5 ml dioxane under heating; 0.5 ml of water followed by cesium carbonate (0.259 g, 0.795 mmol) were added. After that [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex (0.019 g, 0.023 mmol) was added and heated to 135° C. for 30 min by microwave. The reaction mixture was filtered over cellulose; washed with dioxane; concentrated; residue was purifed by 24 g silica gel chromatography (gradient elution dichloromethane for 5 min, then 0-10% methanol in dichloromethane during in 25 min, then dichloromethane 9:1 methanol for 10 min) to yield 2-(2-tert-Butyl-dimethyl-silanyloxymethyl)-3-{1-methyl-5-[5-(morpholine-4-carbonyl)-pyridin-2-ylamino]-6-oxo-1,6-dihydro-pyridin-3-yl}-phenyl)-6-(1-methyl-cyclopropyl)-2H-isoquinolin-1-one (0.095 g, 0.13 mmol) MS (ESI) 732.2 (M+H)+

Workup

  1. temperatureunder heating
  2. additionwere added
  3. additionAfter that [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex (0.019 g, 0.023 mmol) was added
  4. filtrationThe reaction mixture was filtered over cellulose
  5. washwashed with dioxane
  6. concentrationconcentrated
  7. washgradient elution dichloromethane for 5 min

Sources & evidence

ORD record
ord-b9ee93c48fb840538d90a3d47123916e
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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