Triphenylphosphine → HCID 22624958, compound

HRID 279642Notes

Reaction equation

HRID 279642 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[Cl:13][C:14]1[CH:33]=[CH:32][C:17]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([OH:31])=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][N:20]=2)=[C:16]([F:34])[CH:15]=1.[S:35]1[CH:39]=[CH:38][C:37]([CH2:40]O)=[CH:36]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[ClH:13].[Cl:13][C:14]1[CH:33]=[CH:32][C:17]([NH:18][C:19]2[C:28]3[C:23](=[CH:24][C:25]([O:31][CH2:40][C:37]4[CH:38]=[CH:39][S:35][CH:36]=4)=[C:26]([O:29][CH3:30])[CH:27]=3)[N:22]=[CH:21][N:20]=2)=[C:16]([F:34])[CH:15]=1

Participants

6

Reactant 4

HCID 11776Triphenylphosphine2×HCID 123570Thiophene-3-methanol2×HCID 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 22624958HCID 22624958, compoundYield 43.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Diethyl azodicarboxylate (197 μl, 1.2 mmol) was added dropwise to a solution of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (200 mg, 0.6 mmol), (prepared as described for the starting material in Example 24), 3-thiophenemethanol (107 mg, 0.93 mmol) and triphenylphosphine (328 mg, 1.2 mmol) in methylene chloride (6 ml) cooled at 0° C. The mixture was stirred for 2 hours at ambient temperature and further triphenylphosphine (157 mg, 0.57 mmol), 3-thiophenemethanol (107 mg, 0.93 mmol) and diethyl azodicarboxylate (98.5 μl, 0.59 mmol) were added. The mixture was stirred for 2 hours at ambient temperature and the solvent was removed by evaporation. The residue was dissolved in ethyl acetate and the solution was washed with water and brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/ethyl acetate (4/6). The resulting oil was dissolved in ether and a 5M solution of hydrogen chloride in isopropanol (1 ml) was added. The resulting precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-((3-thienyl)methoxy)quinazoline hydrochloride (59 mg, 20%).

Workup

  1. custom(prepared
  2. stirringThe mixture was stirred for 2 hours at ambient temperature
  3. customthe solvent was removed by evaporation
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washthe solution was washed with water and brine
  6. dry with materialdried (MgSO4)
  7. customthe solvent removed by evaporation
  8. customThe residue was purified by column chromatography
  9. washeluting with methylene chloride/ethyl acetate (4/6)
  10. dissolutionThe resulting oil was dissolved in ether
  11. additiona 5M solution of hydrogen chloride in isopropanol (1 ml) was added
  12. filtrationThe resulting precipitate was collected by filtration
  13. washwashed with ether
  14. customdried under vacuum

Sources & evidence

ORD record
ord-acea6c5390f64a97834a81b1530cb1a3
Source dataset
uspto-grants-2002_03
Patent number
US06362336B1

Reaction notes

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