Hydrochloric Acid → HCID 136377254, compound

HRID 1411097Notes

Reaction equation

HRID 1411097 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:29])=[C:7]2[C:12](=[C:13](Br)[N:14]=1)[N:11]([CH2:16][CH:17]([CH2:20][CH3:21])[CH2:18][CH3:19])[C:10](=[O:22])[C:9]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[CH:8]2)=[O:4].C([Sn](CCCC)(CCCC)[C:35]1[CH:40]=[CH:39][N:38]=[CH:37][CH:36]=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:29])=[C:7]2[C:12](=[C:13]([C:35]3[CH:40]=[CH:39][N:38]=[CH:37][CH:36]=3)[N:14]=1)[N:11]([CH2:16][CH:17]([CH2:20][CH3:21])[CH2:18][CH3:19])[C:10](=[O:22])[C:9]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[CH:8]2)=[O:4]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 27373184-(Tri-n-butylstannyl)pyridineHCID 86714191HCID 86714191, compound

Product 1

HCID 136377254HCID 136377254, compoundYield 34.5%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

A mixture of 8-bromo-1-(2-ethyl-butyl)-5-hydroxy-2-oxo-3-phenyl-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (89 mg, 0.19 mmol), 4-tributylstannanyl-pyridine (107 mg, 0.29 mmol) and PdCl2(PPh3)2 (27 mg, 0.039 mmol) in 4 mL of DMF was heated at 120° C. for 2.5 h under nitrogen atmosphere. After the mixture was cooled to r.t., EtOAc and brine were added. 1 M HCl was added 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. MS: (+) m/z 458.43 (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-22fc978882744a0c97f32af57441aecf
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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