Dimethylformamide → HCID 71533505, compound

HRID 1774810Notes

Reaction equation

HRID 1774810 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18](Br)[CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:21][N:22]1[C:31]2[C:26](=[CH:27][C:28](B3OC(C)(C)C(C)(C)O3)=[CH:29][CH:30]=2)[CH2:25][CH2:24][C:23]1=[O:41].CN(C=O)C.C([O-])([O-])=O.[Na+].[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>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@H:9]1[CH2:12][O:13][C:14]1[CH:15]=[N:16][CH:17]=[C:18]([C:28]2[CH:27]=[C:26]3[C:31](=[CH:30][CH:29]=2)[N:22]([CH3:21])[C:23](=[O:41])[CH2:24][CH2:25]3)[CH:19]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 10340Sodium CarbonateHCID 10688713(S)-Tert-butyl 2-(((5-bromopyridin-3-YL)oxy)methyl)azetidine-1-carboxylateHCID 722082331-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-2(1H)-one

Product 1

HCID 71533505HCID 71533505, compoundYield 86.1%

Reagents, catalysts & solvents 2

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A sealed tube was charged with (S)-2-(5-bromo-pyridin-3-yloxymethyl)-azetidine-1-carboxylic acid tert-butyl ester (intermediate A-26, 0.260 g, 0.76 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, 0.239 g, 0.83 mmol) and DMF (3 mL). Then, bis(triphenylphosphine)palladium(II)chloride (0.053 g, 0.076 mmol), followed by 1N aqueous Na2CO3 solution (2.27 mL, 2.27 mmol) were added and the reaction was heated to 110° C. (pre-heated oil bath) for 1 h. The mixture was diluted with EtOAc, filtered through Dicalite and washed with EtOAc (20 mL). The resulting filtrate was poured into aq. NaHCO3 (20 mL) and the aqueous layer was extracted with EtOAc (20 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 100% EtOAc-heptane gradient to give the title compound (0.277 g, 86%) as a light brown foam. MS: 424.1 (M+H+).

Workup

  1. additionwere added
  2. temperature(pre-heated oil bath) for 1 h
  3. filtrationfiltered through Dicalite
  4. washwashed with EtOAc (20 mL)
  5. additionThe resulting filtrate was poured into aq. NaHCO3 (20 mL)
  6. extractionthe aqueous layer was extracted with EtOAc (20 mL)
  7. washCombined organics were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by silica gel flash chromatography
  12. washeluting with a 0 to 100% EtOAc-heptane gradient

Sources & evidence

ORD record
ord-ca8afb058b6d40b19644e0af129a16d5
Source dataset
uspto-grants-2016_02
Patent number
US09260408B2

Reaction notes

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