Sodium Carbonate → HCID 117667619, compound

HRID 712683Notes

Reaction equation

HRID 712683 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14](Br)=[CH:15][N:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:19]([C:21]1[CH:22]=[C:23](B2OC(C)(C)C(C)(C)O2)[CH:24]=[N:25][CH:26]=1)=[O:20].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:1]([O:5][C:6]([N:8]1[C:17]2[C:12](=[CH:13][C:14]([C:23]3[CH:24]=[N:25][CH:26]=[C:21]([CH:19]=[O:20])[CH:22]=3)=[CH:15][N:16]=2)[CH2:11][CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 49926405-(Tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-3-carbaldehydeHCID 11833959tert-Butyl 6-bromo-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxylate

Product 1

HCID 117667619HCID 117667619, compoundYield 79.9%

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 vial containing 6-bromo-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester (3.35 g, 10.7 mmol), 5-formylpyridine-3-boronic acid pinacol ester (2.74 g, 11.8 mmol), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium (II) (870 mg, 1.1 mmol), and aqueous sodium carbonate solution (2M, 7.5 mL, 15.0 mmol) in 1,4-dioxane (75 mL) is flushed with Ar, sealed tightly and heated to 100° C. for 1 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 on silica gel column (25-100% EtOAc in heptane) to afford 6-(5-formyl-pyridin-3-yl)-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester (2.9 g).

Workup

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

Sources & evidence

ORD record
ord-42326b9cc4f044d0930e9f911f56df9f
Source dataset
uspto-grants-2015_11
Patent number
US09181272B2

Reaction notes

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