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Potassium Iodide → 6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-{[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]methoxy}quinazoline

HRID 1668675
Notes
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Reaction equation

HRID 1668675 reaction equation
Cl[CH2:2][C:3]([N:5]1[CH2:10][CH2:9][CH:8]([CH2:11][O:12][C:13]2[CH:22]=[C:21]3[C:16]([C:17]([O:23][C:24]4[CH:25]=[C:26]5[C:30](=[CH:31][CH:32]=4)[NH:29][CH:28]=[C:27]5[CH3:33])=[N:18][CH:19]=[N:20]3)=[CH:15][C:14]=2[O:34][CH3:35])[CH2:7][CH2:6]1)=[O:4].[NH:36]1[CH2:40][CH2:39][CH2:38][CH2:37]1.[I-].[K+]>CN(C=O)C>[CH3:35][O:34][C:14]1[CH:15]=[C:16]2[C:21](=[CH:22][C:13]=1[O:12][CH2:11][CH:8]1[CH2:9][CH2:10][N:5]([C:3](=[O:4])[CH2:2][N:36]3[CH2:40][CH2:39][CH2:38][CH2:37]3)[CH2:6][CH2:7]1)[N:20]=[CH:19][N:18]=[C:17]2[O:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][CH:28]=[C:27]2[CH3:33]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 3

HCID 4875Potassium IodideHCID 31268PyrrolidineHCID 596829177-{[1-(chloroacetyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazoline

Product 1

HCID 596829086-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-{[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]methoxy}quinazoline

Reagents, catalysts & solvents 1

HCID 6228
Dimethylformamide
Solvent

Conditions

Temperature
80 °C

Procedure

A mixture of 7-{[1-(chloroacetyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazoline (0.118 g), pyrrolidine (0.059 ml), potassium iodide (0.01 g) and DMF (3 ml) was stirred and heated to 80° C. for 40 minutes. The mixture was cooled to ambient temperature, the solvent was removed by evaporation under vacuum and the residue was purified by column chromatography on silica using increasingly polar solvent mixtures, starting with dichloromethane and ending dichloromethane/methanol saturated with ammonia (3.5M) (94/6). Evaporation of the solvents gave a foam which was triturated under ether/pentane (70/30) to give a solid which was collected by filtration and dried under vacuum to give 6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-{[1-(pyrrolidin-1-ylacetyl)piperidin-4-yl]methoxy}quinazoline (0.096 g).

Workup

  1. temperatureThe mixture was cooled to ambient temperature
  2. customthe solvent was removed by evaporation under vacuum
  3. customthe residue was purified by column chromatography on silica using
  4. temperatureincreasingly polar solvent mixtures
  5. customEvaporation of the solvents
  6. customgave a foam which
  7. customwas triturated under ether/pentane (70/30)
  8. customto give a solid which
  9. filtrationwas collected by filtration
  10. customdried under vacuum

Sources & evidence

ORD record
ord-2100e3c2c3854df9aabd9a30749158f1
Source dataset
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07989460B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes