HCID 67415371, compound → HCID 136383504, compound

HRID 1175073Notes

Reaction equation

HRID 1175073 reaction equation
Cl.C([O:9][C:10]1[CH:19]=[C:18]2[C:13]([C:14]([NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[C:22]=3[F:28])=[N:15][CH:16]=[N:17]2)=[CH:12][C:11]=1[O:29][CH3:30])C1C=CC=CC=1>FC(F)(F)C(O)=O>[Cl:27][C:23]1[C:22]([F:28])=[C:21]([NH:20][C:14]2[C:13]3[C:18](=[CH:19][C:10]([OH:9])=[C:11]([O:29][CH3:30])[CH:12]=3)[N:17]=[CH:16][N:15]=2)[CH:26]=[CH:25][CH:24]=1

Participants

3

Reactant 1

HCID 67415371HCID 67415371, compound

Product 1

HCID 136383504HCID 136383504, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 7-(benzyloxy)-N-(3-chloro-2-fluorophenyl)-6-methoxyquinazolin-4-amine hydrochloride 2 (85.45 g, 0.192 mol) in trifluoroacetic acid (300 mL) was heated at 80° C. for 1 hour. The reaction mixture was the evaporated to dryness and the residues re-dissolved in methanol (200 mL). This solution was then added dropwise to a stirred aqueous solution of saturated sodium bicarbonate (500 mL). The resulting precipitate was collected by filtration, washed with acetonitrile and dried under vacuum. The crude solids were then purified by hot (100° C.) trituration with a mixture of butanone (500 mL) and MeOH (100 mL), filtered and dried to 4-[(3-chloro-2-fluorophenyl)amino]-6-methoxyquinazolin-7-ol 3 as a cream solid (45 g, 73%); 1H NMR Spectrum: (DMSO d6): 3.98 (s, 3H), 7.10 (s, 1H), 7.25-7.30 (m, 1H), 7.40-7.50 (m, 1H), 7.50-7.60 (m, 1H), 7.80 (s, 1H), 8.30 (s, 1H), 9.55 (s, 1H), 10.32 (s, 1H); Mass Spectrum: (M+H)+ 319.98

Workup

  1. customevaporated to dryness
  2. dissolutionthe residues re-dissolved in methanol (200 mL)
  3. additionThis solution was then added dropwise to a stirred aqueous solution of saturated sodium bicarbonate (500 mL)
  4. filtrationThe resulting precipitate was collected by filtration
  5. washwashed with acetonitrile
  6. customdried under vacuum
  7. customThe crude solids were then purified by hot (100° C.) trituration with a mixture of butanone (500 mL) and MeOH (100 mL)
  8. filtrationfiltered
  9. dry with materialdried to 4-[(3-chloro-2-fluorophenyl)amino]-6-methoxyquinazolin-7-ol 3 as a cream solid (45 g, 73%)

Sources & evidence

ORD record
ord-16271a6275f14d8f985851010f38f3f4
Source dataset
uspto-grants-2010_11
Patent number
US07838530B2

Reaction notes

Loading…