1-Propanol → 4-(4-Chloro-2-fluoroanilino)-6-methoxyquinazoline

HRID 2182554Notes

Reaction equation

HRID 2182554 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:20][C:21]1[CH:40]=[CH:39][C:24]([NH:25][C:26]2[C:35]3[C:30](=[CH:31][C:32](O)=[C:33]([O:36][CH3:37])[CH:34]=3)[N:29]=[CH:28][N:27]=2)=[C:23]([F:41])[CH:22]=1.C(O)CC.N(C(OCC)=O)=NC(OCC)=O>C(Cl)Cl>[Cl:20][C:21]1[CH:40]=[CH:39][C:24]([NH:25][C:26]2[C:35]3[C:30](=[CH:31][CH:32]=[C:33]([O:36][CH3:37])[CH:34]=3)[N:29]=[CH:28][N:27]=2)=[C:23]([F:41])[CH:22]=1

Participants

6

Reactant 4

HCID 10311-PropanolHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 865864644-(4-Chloro-2-fluoroanilino)-6-methoxyquinazolineYield 65.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

Triphenylphosphine (2.46 g, 9.3 mmol) was added to a suspension of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (1.0 g, 3.1 mmol), (prepared as described for the starting material in Example 2), in methylene chloride (25 ml) and the suspension stirred at 0° C. for 30 minutes. A solution of 3-N-tert-butoxycarbonylamino)-1-propanol (0.65 g, 3.7 mmol) in methylene chloride (3 ml) was added and then diethyl azodicarboxylate (1.47 ml, 7.6 mmol) was added dropwise. The reaction mixture was allowed to warm to ambient temperature and stirred for 18 hours. The reaction mixture was diluted with methylene chloride and washed with aqueous sodium hydrogen carbonate solution, water and then brine. The resultant solution was dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol/triethylamine (100/0/0 and then 95/4/1) to give 7-(3-N-tert-butoxycarbonylamino)propoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (620 mg, 42%).

Workup

  1. custom(prepared
  2. temperatureto warm to ambient temperature
  3. stirringstirred for 18 hours
  4. washwashed with aqueous sodium hydrogen carbonate solution, water
  5. dry with materialThe resultant solution was dried (MgSO4)
  6. customthe solvent removed by evaporation
  7. customThe residue was purified by column chromatography
  8. washeluting with methylene chloride/methanol/triethylamine (100/0/0

Sources & evidence

ORD record
ord-7eff296977834f24aed6f755e8d6f867
Source dataset
uspto-grants-2005_05
Patent number
US06897210B2

Reaction notes

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