Potassium Carbonate → 7-(3-(1,1-Dioxothiomorpholino)propoxy)-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline

HRID 1791789Notes

Reaction equation

HRID 1791789 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+].S(C1C=CC(C)=CC=1)(OO[CH2:36][CH2:37][CH2:38][N:39]1[CH2:44][CH2:43][S:42](=[O:46])(=[O:45])[CH2:41][CH2:40]1)(=O)=O>CN(C=O)C>[O:46]=[S:42]1(=[O:45])[CH2:43][CH2:44][N:39]([CH2:38][CH2:37][CH2:36][O:1][C:2]2[CH:11]=[C:10]3[C:5]([C:6]([O:12][C:13]4[CH:14]=[C:15]5[C:19](=[CH:20][CH:21]=4)[NH:18][CH:17]=[C:16]5[CH3:22])=[N:7][CH:8]=[N:9]3)=[CH:4][C:3]=2[O:23][CH3:24])[CH2:40][CH2:41]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 876873553-(1,1-Dioxothiomorphlino)propoxy tosylateHCID 1357631157-Hydroxy-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline

Product 1

HCID 220306597-(3-(1,1-Dioxothiomorpholino)propoxy)-6-methoxy-4-(3-methylindol-5-yloxy)quinazolineYield 56.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
75 °C

Procedure

A mixture of 7-hydroxy-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline (600 mg, 1.87 mmol), (prepared as described for the starting material in Example 271), potassium carbonate (773 mg, 5.60 mmol) and 3-(1,1-dioxothiomorphlino)propoxy tosylate (1.296 g, 3.74 mmol) in DMF (30 ml) was stirred at 75° C. overnight and allowed to cool to ambient temperature. The reaction mixture was filtered and the solvent removed 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 recrystallised from ethanol to give 7-(3-(1,1-dioxothiomorpholino)propoxy)-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline (525 mg, 56%).

Workup

  1. custom(prepared
  2. temperatureto cool to ambient temperature
  3. filtrationThe reaction mixture was filtered
  4. customthe solvent removed 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 recrystallised from ethanol

Sources & evidence

ORD record
ord-233237a2c74449d28a2d406ee16b0bd3
Source dataset
uspto-grants-2006_07
Patent number
US07074800B1

Reaction notes

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