Hydrochloric Acid → 2-(5-((7-(3-Chloropropoxy)quinazolin-4-yl)amino)-1H-pyrazol-3-yl)acetic acid

HRID 749180Notes

Reaction equation

HRID 749180 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:12][CH2:13][CH2:14][CH2:15][Cl:16])=[CH:9][CH:10]=2)[N:5]=[CH:4][N:3]=1.[NH2:17][C:18]1[CH:22]=[C:21]([CH2:23][C:24]([OH:26])=[O:25])[NH:20][N:19]=1.Cl.O1CCOCC1>CN(C)C=O.O>[Cl:16][CH2:15][CH2:14][CH2:13][O:12][C:8]1[CH:7]=[C:6]2[C:11]([C:2]([NH:17][C:18]3[CH:22]=[C:21]([CH2:23][C:24]([OH:26])=[O:25])[NH:20][N:19]=3)=[N:3][CH:4]=[N:5]2)=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 16221512(5-Amino-2H-pyrazol-3-yl)-acetic acidHCID 162215144-Chloro-7-(3-chloropropoxy)quinazoline

Product 1

HCID 162214512-(5-((7-(3-Chloropropoxy)quinazolin-4-yl)amino)-1H-pyrazol-3-yl)acetic acidYield 82%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

4-chloro-7-(3-chloropropoxy)quinazoline (2.5 g, 9.72 mmol) and (3-amino-1H-pyrazol-5-yl)acetic acid (1.37 g, 9.72 mmol) were combined in dimethylformamide (25 ml). A solution of 4M HCl in dioxane (1.25 ml, 4.8 mmol) was added and the reaction heated to 90° C. for 40 minutes. The solution was cooled to room temperature, diluted with water (250 ml) and filtered through celite. The acidic solution was basified to pH 4.9 and the yellow powder filtered. (At pH 3, a red solid precipitated which was isolated, suspended in water and basified to pH 12. Careful adjustment back to pH 4.8 resulted in the precipitation of a yellow powder, which was combined with the first crop). The solid was washed with diethyl ether and dried over phosphorus pentoxide to yield (3-{[7-(3-chloropropoxy)quinazolin-4-yl]amino}-1H-pyrazol-5-yl)acetic acid as a pale orange solid (2.88 g, 82% yield):

Workup

  1. temperatureThe solution was cooled to room temperature
  2. filtrationfiltered through celite
  3. filtrationthe yellow powder filtered
  4. custom(At pH 3, a red solid precipitated which
  5. customwas isolated
  6. customCareful adjustment back to pH 4.8 resulted in the precipitation of a yellow powder, which
  7. washThe solid was washed with diethyl ether
  8. dry with materialdried over phosphorus pentoxide

Sources & evidence

ORD record
ord-210e443a9d9b490585761bbcb70c1196
Source dataset
uspto-grants-2008_07
Patent number
US07402585B2

Reaction notes

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