Hydrochloric Acid → 1-Benzyl-5-hydroxy-8-methyl-2-oxo-1,2,3,4-tetrahydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

HRID 1410679Notes

Reaction equation

HRID 1410679 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([OH:24])=[C:7]2[C:12](=[C:13](Br)[N:14]=1)[N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:10](=[O:23])[CH2:9][CH2:8]2)=[O:4].[CH3:25][Sn](C)(C)C.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](=[C:13]([CH3:25])[N:14]=1)[N:11]([CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:10](=[O:23])[CH2:9][CH2:8]2)=[O:4]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 11661TetramethyltinHCID 867141051-Benzyl-8-bromo-5-hydroxy-2-oxo-1,2,3,4-tetrahydro-[1,7]naphthyridine-6-carboxylic acid methyl ester

Product 1

HCID 682976681-Benzyl-5-hydroxy-8-methyl-2-oxo-1,2,3,4-tetrahydro-[1,7]naphthyridine-6-carboxylic acid methyl esterYield 79.5%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

A mixture of 1-benzyl-8-bromo-5-hydroxy-2-oxo-1,2,3,4-tetrahydro-[1,7]naphthyridine-6-carboxylic acid methyl ester (145 mg, 0.37 mmol), tetramethyltin (0.3 mL, 1.85 mmol), and PdCl2(PPh3)2 (52 mg, 0.074 mmol) in DMF (5 mL) was heated at 120° C. under nitrogen atmosphere for 2 h. After the mixture was cooled to r.t., EtOAc (50 mL) and brine (10 mL) were added. 1M HCl was added until pH about 3. The aqueous layer was extracted with additional EtOAc, and the organic layers were combined and washed with water and dried over MgSO4. After the solvent was evaporated in vacuo, the crude product was chromatographed (0-60% EtOAc/hexanes+2% AcOH) to give 96 mg of the title compound. MS: (+) m/z 327.11 (M+1).

Workup

  1. temperatureAfter the mixture was cooled to r.t.
  2. extractionThe aqueous layer was extracted with additional EtOAc
  3. washwashed with water
  4. dry with materialdried over MgSO4
  5. customAfter the solvent was evaporated in vacuo
  6. customthe crude product was chromatographed (0-60% EtOAc/hexanes+2% AcOH)

Sources & evidence

ORD record
ord-5929cd9ff71847f6890c944fe08838f6
Source dataset
uspto-grants-2014_12
Patent number
US08921389B2

Reaction notes

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