Potassium Carbonate → 6-Methoxy-4-(3-methylindol-5-yloxy)-7-(3-morpholinopropoxy)quinazoline

HRID 454267Notes

Reaction equation

HRID 454267 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][CH:17]=[C:16]4[CH3:22])=[N:7][CH:8]=[N:9]2)=[CH:4][C:3]=1[O:23][CH3:24].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:32][CH2:33][CH2:34][N:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>CN(C=O)C>[CH3:24][O:23][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[O:1][CH2:32][CH2:33][CH2:34][N:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1)[N:9]=[CH:8][N:7]=[C:6]2[O:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[NH:18][CH:17]=[C:16]2[CH3:22]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 958344-(3-Chloropropyl)morpholineHCID 1357631157-Hydroxy-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline

Product 1

HCID 220309516-Methoxy-4-(3-methylindol-5-yloxy)-7-(3-morpholinopropoxy)quinazolineYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 7-hydroxy-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline (800 mg, 2.49 mmol), (prepared as described in Example 271), potassium carbonate (687 mg, 4.98 mmol) and 1-chloro-3-morpholinopropane (448 mg, 2.74 mmol), (prepared as described for the starting material in Example 1), in DMF (20 ml) was stirred at 80° C. for 2 hours and allowed to cool to ambient temperature. The reaction mixture was filtered and the filtrate evaporated in vacuo. The residue was purified by silica column chromatography, gradient elution (dichloromethane, 5% methanol/95% dichloromethane, methanol/dichloromethane/0.880 saturated aqueous ammonia (100/8/1)) and the product was recrystallised from ethanol to give 6-methoxy-4-(3-methylindol-5-yloxy)-7-(3-morpholinopropoxy)quinazoline (570 mg, 51%).

Workup

  1. custom(prepared
  2. temperatureto cool to ambient temperature
  3. filtrationThe reaction mixture was filtered
  4. customthe filtrate evaporated in vacuo
  5. customThe residue was purified by silica column chromatography, gradient elution (dichloromethane, 5% methanol/95% dichloromethane, methanol/dichloromethane/0.880 saturated aqueous ammonia (100/8/1))
  6. customthe product was recrystallised from ethanol

Sources & evidence

ORD record
ord-918c255bb9664bdeb3723e8625984193
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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