Hydrochloric Acid → HCID 66745832, compound

HRID 2111432Notes

Reaction equation

HRID 2111432 reaction equation
Cl[C:2]1[N:3]=[CH:4][C:5]2[N:14]([CH3:15])[C:13](=[O:16])[CH:12]3[CH:8]([CH2:9][CH2:10][CH2:11]3)[N:7]([CH:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)[C:6]=2[N:22]=1.[NH2:23][C:24]1[CH:32]=[CH:31][C:27]([C:28]([OH:30])=[O:29])=[CH:26][C:25]=1[O:33][CH3:34].Cl.[OH-].[Na+]>C(OCC)(=O)C.C(O)C>[CH:17]1([N:7]2[C:6]3[N:22]=[C:2]([NH:23][C:24]4[CH:32]=[CH:31][C:27]([C:28]([OH:30])=[O:29])=[CH:26][C:25]=4[O:33][CH3:34])[N:3]=[CH:4][C:5]=3[N:14]([CH3:15])[C:13](=[O:16])[CH:12]3[CH:8]2[CH2:9][CH2:10][CH2:11]3)[CH2:21][CH2:20][CH2:19][CH2:18]1

Participants

7

Reactant 4

HCID 313Hydrochloric Acid2×HCID 14798Sodium HydroxideHCID 2880572486-69-3HCID 87576195HCID 87576195, compound

Product 1

HCID 66745832HCID 66745832, compoundYield 34.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 0.580 g (0.0018 mole) of (rac)-6-chloro-4-cyclopentyl-9-methyl-2,3,3a,4,9,10a-hexahydro-1H-4,5,7,9-tetraazabenzo[f]azulen-10-one (VII-68), 0.372 g (0.0022 mole) of 4-amino-3-methoxybenzoic acid, 36.97 mL of ethanol and 0.468 mL of hydrochloric acid was heated at reflux overnight. Additional ethanol and hydrochloric acid were added and the mixture heated at reflux overnight. The mixture was then cooled, made basic to dissolve solids by the addition of sodium hydroxide solution, transferred to a separatory funnel with ethyl acetate. The aqueous layer was washed twice with ethyl acetate, and then acidified by the addition of 1 M hydrochloric acid. The acidified aqueous layer was extracted twice with ethyl acetate and these extracts were combined, washed successively with water and then brine, dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 0.277 g of (rac)-4-(4-cyclopentyl-9-methyl-10-oxo-1,2,3,3a,4,9,10,10a-octahydro-4,5,7,9-tetraaza-benzo[f]azulen-6-ylamino)-3-methoxy-benzoic acid, which was used in the next step without further purification.

Workup

  1. temperaturewas heated
  2. temperatureat reflux overnight
  3. temperaturethe mixture heated
  4. temperatureat reflux overnight
  5. temperatureThe mixture was then cooled
  6. dissolutionto dissolve solids
  7. washThe aqueous layer was washed twice with ethyl acetate
  8. additionacidified by the addition of 1 M hydrochloric acid
  9. extractionThe acidified aqueous layer was extracted twice with ethyl acetate
  10. washwashed successively with water
  11. dry with materialbrine, dried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a1d2955690d141ff88eb87934a6e997f
Source dataset
uspto-grants-2009_04
Patent number
US07517873B2

Reaction notes

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