Dimethylamine → 4-(3-Chloro-2-fluoroanilino)-6-[-1-(N,N-dimethylaminoacetyl)piperidin-3-yloxy]-7-methoxyquinazoline

HRID 1948925Notes

Reaction equation

HRID 1948925 reaction equation
Cl[CH2:2][C:3]([N:5]1[CH2:10][CH2:9][CH2:8][CH:7]([O:11][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][C:21]=2[O:22][CH3:23])[N:18]=[CH:17][N:16]=[C:15]3[NH:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([Cl:31])[C:26]=2[F:32])[CH2:6]1)=[O:4].[CH3:33][NH:34][CH3:35]>C(O)C>[Cl:31][C:27]1[C:26]([F:32])=[C:25]([CH:30]=[CH:29][CH:28]=1)[NH:24][C:15]1[C:14]2[C:19](=[CH:20][C:21]([O:22][CH3:23])=[C:12]([O:11][CH:7]3[CH2:8][CH2:9][CH2:10][N:5]([C:3](=[O:4])[CH2:2][N:34]([CH3:35])[CH3:33])[CH2:6]3)[CH:13]=2)[N:18]=[CH:17][N:16]=1

Participants

4

Reactant 2

HCID 674DimethylamineHCID 685236386-[1-(Chloroacetyl)piperidin-3-yloxy]4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline

Product 1

HCID 100057054-(3-Chloro-2-fluoroanilino)-6-[-1-(N,N-dimethylaminoacetyl)piperidin-3-yloxy]-7-methoxyquinazolineYield 39%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

6-[1-(chloroacetyl)piperidin-3-yloxy]-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline (470 mg, 0.98 mmol) was treated with a 33% solution of dimethylamine in ethanol (20 ml) and stirred at room temperature for 3 hours. The solvent was evaporated under vacuum and the residue purified by column chromatography eluting with methylene chloride/methanol (9/1). The fractions containing the expected product were combined and evaporated under vacuum. The residue was re-columned eluting with methylene chloride/methanol (saturated with ammonia) (92/8). The fractions containing the expected product were combined and evaporated to give the title product (185 mg, 39%); 1H NMR Spectrum: (DMSO d6 at 100° C.) 1.40-1.65 (m, 1H); 1.75-1.95 (m, 2H); 2.00-2.30 (m, 7H); 3.05 (dd, 2H); 3.40-3.62 (m, 2H); 3.62-3.75 (m, 1H); 3.88 (dd, 1H); 3.95 (s, 3H); 4.45-4.65 (m, 1H); 7.15-7.30 (m, 2H); 7.30-7.47 (m, 1H); 7.50-7.7 (m, 1H); 7.88 (s, 1H); 8.40 (s, 1H); 9.25 (s, 1H); Mass Spectrum: (M+H)+ 488.

Workup

  1. customThe solvent was evaporated under vacuum
  2. customthe residue purified by column chromatography
  3. washeluting with methylene chloride/methanol (9/1)
  4. additionThe fractions containing the expected product
  5. customevaporated under vacuum
  6. washThe residue was re-columned eluting with methylene chloride/methanol (saturated with ammonia) (92/8)
  7. additionThe fractions containing the expected product
  8. customevaporated

Sources & evidence

ORD record
ord-d8f876f9d022487ca3a4bc08402e608c
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

Loading…