Hydrochloric Acid → HCID 68297617, compound

HRID 919991Notes

Reaction equation

HRID 919991 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:31])=[C:7]2[C:12](=[C:13](Br)[N:14]=1)[N:11]([C@@H:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH3:17])[C:10](=[O:24])[C:9]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[CH:8]2)=[O:4].C([Sn](CCCC)(CCCC)[C:37]1[CH:38]=[N:39][CH:40]=[CH:41][CH:42]=1)CCC.CCOC(C)=O.Cl>CN(C=O)C.[Cl-].[Na+].O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:31])=[C:7]2[C:12](=[C:13]([C:37]3[CH:38]=[N:39][CH:40]=[CH:41][CH:42]=3)[N:14]=1)[N:11]([C@@H:16]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[CH3:17])[C:10](=[O:24])[C:9]([C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[CH:8]2)=[O:4]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 34838483-(Tributylstannyl)pyridineHCID 86714165HCID 86714165, compound

Product 1

HCID 68297617HCID 68297617, compoundYield 41.9%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of (R)-8-bromo-5-hydroxy-2-oxo-3-phenyl-1-(1-phenyl-ethyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (73 mg, 0.15 mmol), 3-tributylstannanyl-pyridine (0.073 mL, 0.23 mmol) and PdCl2(PPh3)2 (21 mg, 0.030 mmol) in 4 mL of DMF was heated at 120° C. for 3 h under nitrogen atmosphere. After the mixture was cooled to r.t., EtOAc and brine were added. 1 M HCl was added with stirring until pH was about 3-4. The aqueous layer was extracted with additional EtOAc, and the combined organic layer was washed with water and dried over MgSO4. After evaporating the solvent in vacuo, the crude product was purified by silica gel chromatography (5-90% EtOAc/hexanes+1% AcOH) to give 30 mg of the title compound as a brown oil. MS: (+) m/z 478.39 (M+1).

Workup

  1. temperatureAfter the mixture was cooled to r.t.
  2. extractionThe aqueous layer was extracted with additional EtOAc
  3. washthe combined organic layer was washed with water
  4. dry with materialdried over MgSO4
  5. customAfter evaporating the solvent in vacuo
  6. customthe crude product was purified by silica gel chromatography (5-90% EtOAc/hexanes+1% AcOH)

Sources & evidence

ORD record
ord-86e7d470d1774768a724528761f89b1a
Source dataset
uspto-grants-2016_03
Patent number
US09271970B2

Reaction notes

Loading…