Hydrazine hydrate (1:1) → 7-(propan-2-yloxy)-3,4-dihydro-2,6-naphthyridin-1(2H)-one

HRID 577542Notes

Reaction equation

HRID 577542 reaction equation
O=C1C2C(=CC=CC=2)C(=O)[N:3]1[CH2:12][CH2:13][C:14]1[C:15]([C:24]([O:26]C)=O)=[CH:16][C:17]([O:20][CH:21]([CH3:23])[CH3:22])=[N:18][CH:19]=1.O.NN>CCO>[CH3:22][CH:21]([O:20][C:17]1[CH:16]=[C:15]2[C:14]([CH2:13][CH2:12][NH:3][C:24]2=[O:26])=[CH:19][N:18]=1)[CH3:23]

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 86723771methyl 5-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-2-(propan-2-yloxy)pyridine-4-carboxylate

Product 1

HCID 867237727-(propan-2-yloxy)-3,4-dihydro-2,6-naphthyridin-1(2H)-oneYield 96%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To methyl 5-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-2-(propan-2-yloxy)pyridine-4-carboxylate (112c, 0.630 g, 1.71 mmol) in EtOH (50 mL) was added hydrazine monohydrate (0.850 mL, 17.1 mmol). The reaction mixture was refluxed for 5 hours. The reaction mixture was cooled to room temperature and the white solids collected by filtration and rinsed with EtOH. The mother liquor was concentrated and H2O (25 mL) was added, then the aqueous layer extracted with EtOAc (3×25 mL) The combined organic layers were concentrated under vacuum and purified by column chromatography (0-80% ethyl acetate/heptanes) to give 7-(propan-2-yloxy)-3,4-dihydro-2,6-naphthyridin-1(2H)-one (112d, 337 mg, 96%) as a white solid.

Workup

  1. temperatureThe reaction mixture was refluxed for 5 hours
  2. filtrationthe white solids collected by filtration
  3. washrinsed with EtOH
  4. concentrationThe mother liquor was concentrated
  5. additionH2O (25 mL) was added
  6. extractionthe aqueous layer extracted with EtOAc (3×25 mL) The combined organic layers
  7. concentrationwere concentrated under vacuum
  8. custompurified by column chromatography (0-80% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-890cf07215974bcbabfc3c27a03aeb14
Source dataset
uspto-grants-2015_05
Patent number
US09040515B2

Reaction notes

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