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

HRID 454270Notes

Reaction equation

HRID 454270 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-394cd49f7bcc4ad98da0874d7b0c15f3
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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