Potassium Carbonate → 6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)-4-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)quinazoline

HRID 454176Notes

Reaction equation

HRID 454176 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[OH:23][C:24]1[CH:25]=[C:26]2[CH:32]=[CH:31][NH:30][C:27]2=[N:28][CH:29]=1.C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>CN(C=O)C.ClCCl.CO>[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:22][CH2:21][CH2:20][CH2:19]1)[N:5]=[CH:4][N:3]=[C:2]2[O:23][C:24]1[CH:25]=[C:26]2[CH:32]=[CH:31][NH:30][C:27]2=[N:28][CH:29]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 111417924-Chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazolineHCID 220307221H-Pyrrolo[2,3-b]pyridin-5-ol

Product 1

HCID 220305886-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)-4-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)quinazolineYield 18%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (218 mg, 0.68 mmol), (prepared as described for the starting material in Example 9), 5-hydroxy-1H-pyrrolo[2,3-b]pyridine (100 mg, 0.75 mmol) and potassium carbonate (280 mg, 2.0 mmol) in DMF (4 ml) was stirred at 95° C. for 6 hours and allowed to cool to ambient temperature. The reaction mixture was treated with 1.0 N aqueous sodium hydroxide solution and allowed to stir at ambient temperature for a few minutes. The resulting precipitate was filtered off, washed with water and air dried to give a crude product which was purified by column chromatography, eluting with dichloromethane/methanol/880 ammonia (100/8/1). The relevant fractions were combined and evaporated ‘in vacuo’ to give a white solid. This was recolumned using dichloromethane/methanol (4/1) solvent to give a white solid which was triturated with acetone, filtered and dried to give 6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)-4-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)quinazoline (50 mg, 18%).

Workup

  1. custom(prepared
  2. temperatureto cool to ambient temperature
  3. stirringto stir at ambient temperature for a few minutes
  4. filtrationThe resulting precipitate was filtered off
  5. washwashed with water and air
  6. customdried
  7. customto give a crude product which
  8. customwas purified by column chromatography
  9. washeluting with dichloromethane/methanol/880 ammonia (100/8/1)
  10. customevaporated ‘in vacuo’
  11. customto give a white solid
  12. customto give a white solid which
  13. customwas triturated with acetone
  14. filtrationfiltered
  15. customdried

Sources & evidence

ORD record
ord-96289797cebf423f84cb023bffb4bb13
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

Loading…