Sodium Carbonate → HCID 117667637, compound

HRID 712689Notes

Reaction equation

HRID 712689 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8](=[O:10])[CH3:9])[CH:5]=[N:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].[C:34]([O:38][C:39]([N:41]1[C:50]2[C:45](=[CH:46][C:47](Br)=[CH:48][N:49]=2)[CH2:44][CH2:43][CH2:42]1)=[O:40])([CH3:37])([CH3:36])[CH3:35].C(=O)([O-])[O-].[Na+].[Na+]>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]>[C:34]([O:38][C:39]([N:41]1[C:50]2[C:45](=[CH:46][C:47]([C:2]3[CH:7]=[N:6][CH:5]=[C:4]([C:8](=[O:10])[CH3:9])[CH:3]=3)=[CH:48][N:49]=2)[CH2:44][CH2:43][CH2:42]1)=[O:40])([CH3:37])([CH3:35])[CH3:36]

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 8204233-Acetyl-5-bromopyridineHCID 2733548Bis(pinacolato)diboraneHCID 11833959tert-Butyl 6-bromo-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

Product 1

HCID 117667637HCID 117667637, compoundYield 79.3%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
70 °C

Procedure

A vial containing 1-(5-bromo-pyridin-3-yl)-ethanone (1.59 g, 8.0 mmol), bis(pinacolato)diboron (2.53 g, 9.9 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) DCM complex (486 mg, 0.66 mmol) and potassium acetate (1.96 g, 19.9 mmol) in 1,4-dioxane (100 mL) is flushed with Ar, sealed tightly and heated to 70° C. for 16 h. The reaction mixture is cooled to room temperature and 6-bromo-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester (2.08 g, 6.6 mmol), aqueous sodium carbonate solution (2M, 9.9 mL, 19.9 mmol) and additional 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium (II) (486 mg, 0.66 mmol) are added. The mixture is flushed with Ar, sealed tightly and heated to 100° C. for 2 h. The reaction mixture is cooled to room temperature and partitioned between water and EtOAc. The layers are separated and the aqueous is further extracted with EtOAc. The combined organic layers are washed with brine and filtered through diatomaceous earth, rinsing well with EtOAc. The filtrate is dried (Na2SO4) and concentrated. The crude product is purified by silica gel column (25-100% EtOAc in heptane) to afford 6-(5-acetyl-pyridin-3-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester (1.85 g).

Workup

  1. customis flushed with Ar
  2. customsealed tightly
  3. temperatureThe reaction mixture is cooled to room temperature
  4. customThe mixture is flushed with Ar
  5. customsealed tightly
  6. temperatureheated to 100° C. for 2 h
  7. temperatureThe reaction mixture is cooled to room temperature
  8. custompartitioned between water and EtOAc
  9. customThe layers are separated
  10. extractionthe aqueous is further extracted with EtOAc
  11. washThe combined organic layers are washed with brine
  12. filtrationfiltered through diatomaceous earth
  13. washrinsing well with EtOAc
  14. dry with materialThe filtrate is dried (Na2SO4)
  15. concentrationconcentrated
  16. customThe crude product is purified by silica gel column (25-100% EtOAc in heptane)

Sources & evidence

ORD record
ord-edf43368b2a14681b669d04a058c6e5d
Source dataset
uspto-grants-2015_11
Patent number
US09181272B2

Reaction notes

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