Hydrochloric Acid → HCID 17942742, compound

HRID 855732Notes

Reaction equation

HRID 855732 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[CH2:24]([C:28]1[CH2:32][C:31](=[O:33])[NH:30][N:29]=1)[CH:25]([CH3:27])[CH3:26].C(=O)([O-])[O-].[K+].[K+].Cl>CN(C=O)C.C(OCC)(=O)C.O>[CH2:24]([C:28]1[NH:29][N:30]=[C:31]([O:33][C:2]2[C:11]3[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]4[CH2:23][CH2:22][O:21][CH2:20][CH2:19]4)=[C:9]([O:12][CH3:13])[CH:10]=3)[N:5]=[CH:4][N:3]=2)[CH:32]=1)[CH:25]([CH3:27])[CH3:26]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 5207142,4-Dihydro-5-(2-methylpropyl)-3H-pyrazol-3-oneHCID 118239414-Chloro-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinazoline

Product 1

HCID 17942742HCID 17942742, compoundYield 43%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (150 mg, 0.44 mol), (prepared as described for the starting material in Example 2), and 3-isobutyl-4,5-dihydro-1H-pyrazol-5-one (75 mg, 0.53 mol), (Org. Synth. 1976, 55, 73), in DMF (2 ml) containing potassium carbonate (92 mg, 0.67 mol) was heated at 100° C. for 2.5 hours. After cooling, water was added and the aqueous layer was adjusted to pH6.5 with 2M hydrochloric acid. Ethyl acetate was added. The organic layer was separated, washed with water, brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was purified by column chromatography eluting the ethyl acetate/methylene chloride (1/1) followed by methanol/ethyl acetate/methylene chloride (1/4/5) and by methanol/methylene chloride (1/9) to give 4-(5-isobutylpyrazol-3-yloxy)-6-methoxy-7-(3-morpholinopropoxy)quinazoline (85 mg, 43%).

Workup

  1. custom(prepared
  2. temperatureAfter cooling
  3. customThe organic layer was separated
  4. washwashed with water, brine
  5. dry with materialdried (MgSO4)
  6. customthe volatiles were removed by evaporation
  7. customThe residue was purified by column chromatography
  8. washeluting the ethyl acetate/methylene chloride (1/1)

Sources & evidence

ORD record
ord-7e6c7cb7dad542d1b5373cf66f2e568b
Source dataset
uspto-grants-2007_08
Patent number
US07262201B1

Reaction notes

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