Morpholine → HCID 22030567, compound

HRID 1791664Notes

Reaction equation

HRID 1791664 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([CH3:22])=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24].C(=O)([O-])[O-].[K+].[K+].[CH2:31]([CH:33]1[O:35][CH2:34]1)Br.[NH:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1>CN(C=O)C>[OH:35][CH:33]([CH2:34][N:36]1[CH2:41][CH2:40][O:39][CH2:38][CH2:37]1)[CH2:31][O:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([O:12][C:13]3[CH:14]=[C:15]4[C:19](=[CH:20][CH:21]=3)[NH:18][C:17]([CH3:22])=[CH:16]4)=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24]

Participants

6

Reactant 4

HCID 8083MorpholineHCID 11430Potassium CarbonateHCID 18430EpibromohydrinHCID 1357631087-hydroxy-6-methoxy-4-(2-methyl-1H-indol-5-yloxy)quinazoline

Product 1

HCID 22030567HCID 22030567, compoundYield 45.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A mixture of 7-hydroxy-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (322 mg, 1.00 mmol), (prepared as described in Example 49), potassium carbonate (414 mg, 3.00 mmol) and epibromohydrin (274 mg, 2.00 mmol) in DMF (7.0 ml) was stirred at 60° C. for 2 hours and allowed to cool to ambient temperature. The solvent was removed by evaporation and the residue taken up in dichloromethane (10 ml). An aliquot (5 ml) of this solution was treated with morpholine (48 ul, 0.6 mmol) and stirred for 24 hours at ambient temperature. The solvent was removed by evaporation, treated with water and stirred vigorously for 30 minutes. The precipitate was filtered, washed with water and dried. The resultant solid was stirred as a suspension in acetone, filtered, washed with diethyl ether and dried to give 7-(2-hydroxy-3-morpholinopropoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (127 mg, 27%).

Workup

  1. temperatureto cool to ambient temperature
  2. customThe solvent was removed by evaporation
  3. stirringstirred for 24 hours at ambient temperature
  4. customThe solvent was removed by evaporation
  5. additiontreated with water
  6. stirringstirred vigorously for 30 minutes
  7. filtrationThe precipitate was filtered
  8. washwashed with water
  9. customdried
  10. stirringThe resultant solid was stirred as a suspension in acetone
  11. filtrationfiltered
  12. washwashed with diethyl ether
  13. customdried

Sources & evidence

ORD record
ord-b33bc77474b14b988eedcc8eb51a757b
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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