Triphenylphosphine → HCID 22625049, compound

HRID 1384577Notes

Reaction equation

HRID 1384577 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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:54][N:55]1[CH:59]=[CH:58][N:57]=[C:56]1[CH2:60][CH2:61]O>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][CH2:61][CH2:60][C:56]4[N:55]([CH3:54])[CH:59]=[CH:58][N:57]=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 220568ethyl N-ethoxycarbonyliminocarbamate2×HCID 5659642-(1-Methyl-1H-iMidazol-2-yl)ethanolHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 22625049HCID 22625049, compoundYield 73.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (128 μl, 1.5 mmol) was added dropwise to a solution of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (250 mg, 0.78 mmol), (prepared as described for the starting material in Example 24), triphenylphosphine (410 mg, 1.5 mmol) and 2-(1-methylimidazol-2-yl)ethanol (147 mg, 1.15 mmol), (EP 0675112 A1), in methylene chloride (4 ml) and the mixture was stirred for 30 minutes at ambient temperature. Further triphenylphosphine (143 mg, 0.52 mmol) and diethyl azodicarboxylate (85 μl, 1 mmol) were added and the mixture stirred for 1 hour at ambient temperature. The solid product was collected by filtration and washed with methylene chloride. The solid was dissolved in a mixture of methylene chloride (25 ml) and methanol (25 ml), and a solution of 2.9M ethereal hydrogen chloride (2 ml) was added. The mixture was concentrated by evaporation and the resulting precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(1-methylimidazol-2-yl)ethoxy)quinazoline hydrochloride (133 mg, 34%). m.p. 224-229° C. 1H NMR Spectrum: (DMSOd6) 3.62(t, 2H); 3.94(s, 3H); 4.0(s, 3H); 4.59(t, 2H); 7.43(d, 1H); 7.46(s, 1H); 7.6(t, 1H); 7.6-7.7(m, 3H); 8.41(s, 1H); 8.78(s, 1H); 11.75(br s, 1H) MS-ESI: 428 [MH]+

Workup

  1. custom(prepared
  2. stirringthe mixture stirred for 1 hour at ambient temperature
  3. filtrationThe solid product was collected by filtration
  4. washwashed with methylene chloride
  5. dissolutionThe solid was dissolved in a mixture of methylene chloride (25 ml) and methanol (25 ml)
  6. additiona solution of 2.9M ethereal hydrogen chloride (2 ml) was added
  7. concentrationThe mixture was concentrated by evaporation
  8. filtrationthe resulting precipitate was collected by filtration
  9. washwashed with ether
  10. customdried under vacuum

Sources & evidence

ORD record
ord-5929028615564f6f8eb7979a1d3a2778
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

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