Trifluoroacetic acid → 6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-[(piperidin-4-yl)methoxy]quinazoline

HRID 1668674Notes

Reaction equation

HRID 1668674 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][O:15][C:16]2[CH:25]=[C:24]3[C:19]([C:20]([O:26][C:27]4[CH:28]=[C:29]5[C:33](=[CH:34][CH:35]=4)[NH:32][CH:31]=[C:30]5[CH3:36])=[N:21][CH:22]=[N:23]3)=[CH:18][C:17]=2[O:37][CH3:38])[CH2:10][CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[CH3:38][O:37][C:17]1[CH:18]=[C:19]2[C:24](=[CH:25][C:16]=1[O:15][CH2:14][CH:11]1[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]1)[N:23]=[CH:22][N:21]=[C:20]2[O:26][C:27]1[CH:28]=[C:29]2[C:33](=[CH:34][CH:35]=1)[NH:32][CH:31]=[C:30]2[CH3:36]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 220305997-{[1-(tert-butoxycarbonyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazoline

Product 1

HCID 220307946-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-[(piperidin-4-yl)methoxy]quinazolineYield 76.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

7-{[1-(tert-Butoxycarbonyl)piperidin-4-yl]methoxy}-6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]quinazoline (5.8 g) was suspended in dichloromethane (40 ml) and cooled with an ice bath. TFA (17 ml) was added and the reaction mixture was stirred at this temperature for 1 hour. The volatiles were removed under vacuum and the residue triturated under water and dichloromethane. The pH was made basic to 12.5 with a 30% aqueous solution of sodium hydroxide while cooling with an ice bath. Extraction was done with a mixture of dichloromethane and methanol. The combined extracts were washed in turn with water and brine and dried over magnesium sulphate. The solvent was evaporated under vacuum and the residue was triturated under ether, filtered and dried to give 6-methoxy-4-[(3-methyl-1H-indol-5-yl)oxy]-7-[(piperidin-4-yl)methoxy]quinazoline (3.6 g).

Workup

  1. temperaturecooled with an ice bath
  2. customThe volatiles were removed under vacuum
  3. customthe residue triturated under water
  4. temperaturewhile cooling with an ice bath
  5. extractionExtraction
  6. additionwas done with a mixture of dichloromethane and methanol
  7. washThe combined extracts were washed in turn with water and brine
  8. dry with materialdried over magnesium sulphate
  9. customThe solvent was evaporated under vacuum
  10. customthe residue was triturated under ether
  11. filtrationfiltered
  12. customdried

Sources & evidence

ORD record
ord-10bd8474d52c41b89827acedb5b7a113
Source dataset
uspto-grants-2011_08
Patent number
US07989460B2

Reaction notes

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