Formaldehyde → HCID 59371213, compound

HRID 1948955Notes

Reaction equation

HRID 1948955 reaction equation
[Cl:1][C:2]1[C:3]([F:38])=[C:4]([CH:35]=[CH:36][CH:37]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:33][CH3:34])=[C:13]([O:16][C@H:17]3[CH2:21][N:20]([C:22](OC(C)(C)C)=O)[C@H:19]([C:29]([O:31][CH3:32])=[O:30])[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:38])=[C:4]([CH:35]=[CH:36][CH:37]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:33][CH3:34])=[C:13]([O:16][C@H:17]3[CH2:21][N:20]([CH3:22])[CH:19]([C:29]([O:31][CH3:32])=[O:30])[CH2:18]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 60036685HCID 60036685, compound

Product 1

HCID 59371213HCID 59371213, compoundYield 65.3%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
85 °C

Procedure

A solution of 4-(3-chloro-2-fluoroanilino)-6-[(2S,4R)-1-(tert-butoxycarbonyl)-2-(methoxycarbonyl)pyrrolidin-4-yloxy]-7-methoxyquinazoline (480 mg, 0.88 mmol) in formic acid (50 ml) was reacted with paraformaldehyde (29 mg, 0.97 mmol) and the resulting mixture heated at 85° C. for 6 hours. The reaction mixture was evaporated and the residues partitioned between saturated aqueous NaHCO3 (50 ml) and ethyl acetate (100 ml). The organic layer was dried over MgSO4, filtered and evaporated. The residue was purified by flash chromatography on silica eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 90/10). The fractions containing the expected product were combined and evaporated to give 4-(3-chloro-2-fluoroanilino)-6-[(2RS,4R)-1-methyl-2-(methoxycarbonyl)pyrrolidin-4-yloxy]-7-methoxyquinazoline as a white foam (265 mg); Mass Spectrum: (M+H)+ 461.

Workup

  1. customThe reaction mixture was evaporated
  2. customthe residues partitioned between saturated aqueous NaHCO3 (50 ml) and ethyl acetate (100 ml)
  3. dry with materialThe organic layer was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by flash chromatography on silica eluting
  7. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 90/10)
  8. additionThe fractions containing the expected product
  9. customevaporated

Sources & evidence

ORD record
ord-7827db4ce10942c98d0ddcd3f89fa5f7
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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