HCID 178498786, compound → methyl 7-amino-4H-5-oxa-3,9b-diazacyclopenta[a]naphthalene-6-carboxylate

HRID 595121Notes

Reaction equation

HRID 595121 reaction equation
[NH2:1][C:2]1[CH:18]=[CH:17][C:5]2[N:6]=[C:7]([NH:10][CH2:11][CH:12](OC)OC)[CH2:8][O:9][C:4]=2[C:3]=1[C:19]([O:21][CH3:22])=[O:20]>Cl.CO>[NH2:1][C:2]1[CH:18]=[CH:17][C:5]2[N:6]3[CH:12]=[CH:11][N:10]=[C:7]3[CH2:8][O:9][C:4]=2[C:3]=1[C:19]([O:21][CH3:22])=[O:20]

Participants

4

Reactant 1

HCID 178498786HCID 178498786, compound2×

Product 1

HCID 86712824methyl 7-amino-4H-5-oxa-3,9b-diazacyclopenta[a]naphthalene-6-carboxylateYield 53.1%

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

A solution of methyl 7-amino-3-(2,2-dimethoxyethylamino)-2H-benzo[1,4]oxazine-8-carboxylate (Intermediate 27, 0.910 g) in concentrated aqueous hydrochloric acid (8 mL) and methanol (10 mL) was heated to reflux for 3 hours. After cooling, the mixture was concentrated in vacuo and the residue was dissolved in a mixture of ethyl acetate and water and basified with 2M aqueous sodium hydroxide solution. The layers were separated and the aqueous layer was extracted several times with ethyl acetate. The combined organic layers were dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane with a gradient of 50-100% and then a mixture of methanol and ethyl acetate (5%) to give methyl 7-amino-4H-5-oxa-3,9b-diazacyclopenta[a]naphthalene-6-carboxylate (0.383 g) as a sandy coloured solid.

Workup

  1. temperatureto reflux for 3 hours
  2. temperatureAfter cooling
  3. concentrationthe mixture was concentrated in vacuo
  4. dissolutionthe residue was dissolved in a mixture of ethyl acetate and water
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted several times with ethyl acetate
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe residue was purified by chromatography on silica
  11. washeluting with a mixture of ethyl acetate and cyclohexane with a gradient of 50-100%
  12. additiona mixture of methanol and ethyl acetate (5%)

Sources & evidence

ORD record
ord-e9acc8d6dfb74c77a7984d02a66c7324
Source dataset
uspto-grants-2016_01
Patent number
US09242997B2

Reaction notes

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