Ethanol → tert-butyl 6-(6-cyclopropylpyridin-3-yl)-3,4-dihydro-2,7-naphthyridine-2(1H)-carboxylate

HRID 1441488Notes

Reaction equation

HRID 1441488 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][N:16]=1)[CH2:13][N:12]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:11][CH2:10]2)(=O)=O.[CH:26]1([C:29]2[CH:34]=[CH:33][C:32](B3OC(C)(C)C(C)(C)O3)=[CH:31][N:30]=2)[CH2:28][CH2:27]1.C(=O)([O-])[O-].[Na+].[Na+].CCO>O.Cl[Pd]Cl.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.[Fe+2].C1(C)C=CC=CC=1>[CH:26]1([C:29]2[N:30]=[CH:31][C:32]([C:7]3[CH:8]=[C:9]4[C:14](=[CH:15][N:16]=3)[CH2:13][N:12]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:11][CH2:10]4)=[CH:33][CH:34]=2)[CH2:28][CH2:27]1

Participants

9

Reactant 4

HCID 702EthanolHCID 10340Sodium CarbonateHCID 457864292-Cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 86625015tert-Butyl 6-(((trifluoromethyl)sulfonyl)oxy)-3,4-dihydro-2,7-naphthyridine-2(1H)-carboxylate

Product 1

HCID 66734762tert-butyl 6-(6-cyclopropylpyridin-3-yl)-3,4-dihydro-2,7-naphthyridine-2(1H)-carboxylateYield 76.3%

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

tert-Butyl 6-{[(trifluoromethyl)sulfonyl]oxy}-3,4-dihydro-2,7-naphthyridine-2(1H)-carboxylate (0.34 g, 0.90 mmol), 2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.20 g, 0.82 mmol), PdCl2×dppf (0.050 g), saturated sodium carbonate (2 mL), EtOH (4 mL) and toluene (4 mL) were stirred at 80° C. for 2 h. The solution was cooled to RT, taken up in water (15 mL) and extracted three times with EtOAc-Et2O. The combined organic phases were dried, filtered and concentrated. Purification by column chromatography with EtOAc-heptanes (1:1 through 3:1) and EtOAc-MeOH (9:1) as eluents gave 0.22 g (70%) of tert-butyl 6-(6-cyclopropylpyridin-3-yl)-3,4-dihydro-2,7-naphthyridine-2(1H)-carboxylate as a white solid.

Workup

  1. extractionextracted three times with EtOAc-Et2O
  2. customThe combined organic phases were dried
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by column chromatography with EtOAc-heptanes (1:1 through 3:1) and EtOAc-MeOH (9:1) as eluents

Sources & evidence

ORD record
ord-28469a9c105540678c7a34db67883f2b
Source dataset
uspto-grants-2010_02
Patent number
US07655664B2

Reaction notes

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