Trifluoroacetic acid → HCID 22030736, compound

HRID 454080Notes

Reaction equation

HRID 454080 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][N:16](C)[C:17](OC(C)(C)C)=O)[N:9]=[CH:8][N:7]=[C:6]2[O:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][C:30]([CH3:35])=[CH:29]2.C(O)(C(F)(F)F)=O.C(N(CC)CC)C.[CH3:50][S:51](Cl)(=[O:53])=[O:52]>C(Cl)Cl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:12]=1[O:13][CH2:14][CH2:15][N:16]([CH3:17])[S:51]([CH3:50])(=[O:53])=[O:52])[N:9]=[CH:8][N:7]=[C:6]2[O:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][C:30]([CH3:35])=[CH:29]2

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 22030965HCID 22030965, compound

Product 1

HCID 22030736HCID 22030736, compoundYield 38.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A suspension of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(2-(N-methyl-N-tert-butoxycarbonylamino)ethoxy)quinazoline (148 mg, 0.31 mmol), (prepared as described in Example 149), in methylene chloride (4 ml) containing TFA (1 ml) was stirred for 1 hour. After removing the volatiles under vacuum, the residue was azeotroped with toluene. The residue was dissolved in methylene chloride (3 ml) and triethylamine (215 μl, 1.5 mmol) was added followed by methanesulphonyl chloride (48 μl, 0.62 mmol). After stirring for 1 hour at ambient temperature, the mixture was partitioned between methylene chloride and water. The organic layer was separated, washed with water, brine, dried (MgSO4) and evaporated. The residue was purified by column chromatography eluting with ethylacetate/methanol (99/1 followed by 97/3). After evaporation of the solvent, the solid was triturated with ether, filtered, washed with ether and dried under vacuum to give 6-methoxy-4-(2-methylindol-5-yloxy)-7-(2-(N-methyl-N-methylsulphonylamino)ethoxy)quinazoline (54 mg, 38%).

Workup

  1. customAfter removing the volatiles under vacuum
  2. customthe residue was azeotroped with toluene
  3. dissolutionThe residue was dissolved in methylene chloride (3 ml)
  4. stirringAfter stirring for 1 hour at ambient temperature
  5. customthe mixture was partitioned between methylene chloride and water
  6. customThe organic layer was separated
  7. washwashed with water, brine
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customThe residue was purified by column chromatography
  11. washeluting with ethylacetate/methanol (99/1 followed by 97/3)
  12. customAfter evaporation of the solvent
  13. customthe solid was triturated with ether
  14. filtrationfiltered
  15. washwashed with ether
  16. customdried under vacuum

Sources & evidence

ORD record
ord-068853640f12491a9ae36b26ec6e9980
Source dataset
uspto-grants-2013_07
Patent number
US08492560B2

Reaction notes

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