Acetic Acid → HCID 178486771, compound

HRID 454009

Reaction equation

HRID 454009 reaction equation
Cl.[NH2:2][C:3]1[CH:11]=[C:10]([O:12][CH2:13][CH2:14][CH2:15][N:16]2[CH2:20][CH2:19][CH2:18][CH2:17]2)[C:9]([O:21][CH3:22])=[CH:8][C:4]=1[C:5]([NH2:7])=[O:6].[CH3:23]N(C=NC=[N+](C)C)C.[Cl-].C(O)(=O)C.C([O-])(=O)C.[Na+]>O1CCOCC1>[OH:6][C:5]1[C:4]2[C:3](=[CH:11][C:10]([O:12][CH2:13][CH2:14][CH2:15][N:16]3[CH2:20][CH2:19][CH2:18][CH2:17]3)=[C:9]([O:21][CH3:22])[CH:8]=2)[N:2]=[CH:23][N:7]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 517045Sodium AcetateHCID 11008255Gold's ReagentHCID 218748202-Amino-5-methoxy-4-(3-(pyrrolidin-1-yl)propoxy)benzamide hydrochloride

Product 1

HCID 178486771HCID 178486771, compoundYield 92.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 2-amino-5-methoxy-4-(3-(pyrrolidin-1-yl)propoxy)benzamide hydrochloride (5.92 g, 16.2 mmol) and Gold's reagent (3.5 g, 21.4 mmol) in dioxane (50 ml) was heated at reflux for 5 hours. Acetic acid (0.7 ml) and sodium acetate (1.33 g) were added to the reaction mixture which was heated at reflux for a further 5 hours. The mixture was allowed to cool and the volatiles were removed by evaporation. The residue was dissolved in water, adjusted to pH8 with 2M aqueous sodium hydroxide solution and purified on a Diaion (trademark of Mitsubishi) HP20SS resin column eluting with methanol (gradient 0-50%) in water. The fractions containing product were concentrated by evaporation and then freeze dried to give 4-hydroxy-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (4.55 g, 83%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 5 hours
  3. temperaturewas heated
  4. temperatureat reflux for a further 5 hours
  5. temperatureto cool
  6. customthe volatiles were removed by evaporation
  7. dissolutionThe residue was dissolved in water
  8. custompurified on a Diaion (trademark of Mitsubishi) HP20SS resin column
  9. washeluting with methanol (gradient 0-50%) in water
  10. additionThe fractions containing product
  11. concentrationwere concentrated by evaporation
  12. customfreeze dried

Sources & evidence

ORD record
ord-0f4a7da9364d4158b5e49b2651db09fc
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Linked notes

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