Formaldehyde → HCID 10001196, compound

HRID 1948942Notes

Reaction equation

HRID 1948942 reaction equation
[Cl:1][C:2]1[C:3]([F:34])=[C:4]([CH:31]=[CH:32][CH:33]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:29][CH3:30])=[C:13]([O:16][C@H:17]3[CH2:21][CH2:20][N:19]([C:22](OC(C)(C)C)=O)[CH2:18]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1.C=O>C(O)=O>[Cl:1][C:2]1[C:3]([F:34])=[C:4]([CH:31]=[CH:32][CH:33]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:29][CH3:30])=[C:13]([O:16][C@H:17]3[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 68523549HCID 68523549, compound

Product 1

HCID 10001196HCID 10001196, compoundYield 53.8%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
85 °C

Procedure

4-(3-chloro-2-fluoroanilino)-6-[(3S)-1-tert-butoxycarbonylpyrrolidin-3-yloxy]-7-methoxyquinazoline (0.30 g) was dissolved in formic acid (5 ml) and formaldehyde (37% w/v in water) (2.5 ml) was added. The mixture was heated to 85° C. for one hour and then evaporated under vacuum and azeotroped with toluene. The residue was partitioned between ethyl acetate and saturated aqueous NaHCO3. The organic layer was separated, washed with brine, dried over Na2SO4, filtered and evaporated. The residue was purified by column chromatography eluting with increasingly polar mixtures of methylene chloride/methanol (saturated with ammonia) (100/0 to 9416). The fractions containing the expected product were combined, evaporated and the residue triturated with diethylether, filtered and dried under vacuum to give the title product as a white solid (0.133 g; 35%);

Workup

  1. customevaporated under vacuum
  2. customazeotroped with toluene
  3. customThe residue was partitioned between ethyl acetate and saturated aqueous NaHCO3
  4. customThe organic layer was separated
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by column chromatography
  10. washeluting
  11. temperaturewith increasingly polar mixtures of methylene chloride/methanol (saturated with ammonia) (100/0 to 9416)
  12. additionThe fractions containing the expected product
  13. customevaporated
  14. customthe residue triturated with diethylether
  15. filtrationfiltered
  16. customdried under vacuum

Sources & evidence

ORD record
ord-e8dccb66d7c54a35a35239ae8353bf71
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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