Hydrochloric Acid → HCID 68297609, compound

HRID 1410940Notes

Reaction equation

HRID 1410940 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:24])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][CH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)[C:10](=[O:22])[C:9](Br)=[CH:8]2)=[O:4].[C:25]1([Sn](CCCC)(CCCC)CCCC)[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1.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:24])=[C:7]2[C:12](=[CH:13][N:14]=1)[N:11]([CH2:15][CH:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)[C:10](=[O:22])[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 607632TributylphenyltinHCID 68297508HCID 68297508, compound

Product 1

HCID 68297609HCID 68297609, compoundYield 70.4%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
125 °C

Procedure

A mixture of 3-bromo-5-hydroxy-2-oxo-1-(tetrahydro-pyran-4-ylmethyl)-1,2-dihydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (70 mg, 0.18 mmol), PhSnBu3 (0.070 mL, 0.21 mmol), and PdCl2(PPh3)2 (25 mg, 0.035 mmol) in DMF (3 mL) was heated at 125° C. under nitrogen atmosphere for 2 h. After the mixture was cooled to r.t., brine (10 mL) and EtOAc (20 mL) were added. 1 M HCl was added with stirring until pH was about 2. The aqueous layer was extracted with EtOAc, and the organic layers were combined, washed with water, and dried over MgSO4. After evaporating the solvent in vacuo, the crude product was purified twice by silica gel chromatography (0-4% MeOH/CH2Cl2, then 15-100% EtOAc/hexanes+1% AcOH) to give 50 mg of the title compound as a light yellow solid. MS: (+) m/z 395.26 (M+1).

Workup

  1. temperatureAfter the mixture was cooled to r.t.
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washwashed with water
  4. dry with materialdried over MgSO4
  5. customAfter evaporating the solvent in vacuo
  6. customthe crude product was purified twice by silica gel chromatography (0-4% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-3352d2d3804943658de952db6748030d
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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