Sodium Carbonate → HCID 178481475, compound

HRID 1774725Notes

Reaction equation

HRID 1774725 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([N:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[C:13]([CH3:21])([CH3:20])[O:14][SiH2:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH:7]=1.[CH3:22][N:23]1[C:32]2[C:27](=[CH:28][C:29](B3OC(C)(C)C(C)(C)O3)=[CH:30][CH:31]=2)[CH2:26][CH2:25][C:24]1=[O:42].C([O-])([O-])=O.[Na+].[Na+].C([O-])(O)=O.[Na+]>CCOC(C)=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.CN(C=O)C>[C:16]([SiH2:15][O:14][C:13]([CH3:21])([CH3:20])[C@@H:9]1[CH2:10][CH2:11][CH2:12][N:8]1[C:6]1[CH:7]=[C:2]([C:29]2[CH:28]=[C:27]3[C:32](=[CH:31][CH:30]=2)[N:23]([CH3:22])[C:24](=[O:42])[CH2:25][CH2:26]3)[CH:3]=[N:4][CH:5]=1)([CH3:19])([CH3:18])[CH3:17]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 722082331-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-oneHCID 178455458HCID 178455458, compound

Product 1

HCID 178481475HCID 178481475, compoundYield 90.4%

Reagents, catalysts & solvents 3

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vial was charged with 3-bromo-5-[(S)-2-(tert-butyl-dimethyl-silanyloxymethyl)-pyrrolidin-1-yl]-pyridine (0.091 g, 0.245 mmol), 1-methyl-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-3,4-dihydro-1H-quinolin-2-one (intermediate A-1, 0.077 g, 0.270 mmol) and DMF (1.5 mL). The reaction mixture was purged with Argon; then, bis(triphenylphosphine)palladium(II)chloride (0.017 g, 0.025 mmol), followed by a 1N Na2CO3 aqueous solution (0.980 mL, 0.980 mmol) were added and the reaction mixture was heated in the microwave at 120° C. for 30 min. The reaction mixture was diluted with EtOAc, poured into aq. NaHCO3 (10 mL) and the aqueous layer was extracted with EtOAc (2×40 mL). Combined organics were washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by silica gel flash chromatography eluting with a 0 to 5% MeOH-DCM gradient to give the title compound (0.1 g, 90%) as a white solid. MS: 452.1 (M+H+).

Workup

  1. customThe reaction mixture was purged with Argon
  2. additionwere added
  3. extractionthe aqueous layer was extracted with EtOAc (2×40 mL)
  4. washCombined organics were washed with brine
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by silica gel flash chromatography
  9. washeluting with a 0 to 5% MeOH-DCM gradient

Sources & evidence

ORD record
ord-c8f6fb32c61d463094a940190bd4fb57
Source dataset
uspto-grants-2016_02
Patent number
US09260408B2

Reaction notes

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