Triphenylphosphine → HCID 22624908, compound

HRID 1384593Notes

Reaction equation

HRID 1384593 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.[N:54]1[CH:59]=[CH:58][C:57]([NH:60][CH2:61][CH2:62]O)=[CH:56][CH:55]=1>C(Cl)Cl.C(OCC)(=O)C>[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][CH2:62][CH2:61][NH:60][C:57]4[CH:58]=[CH:59][N:54]=[CH:55][CH:56]=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

7

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 177503682-[(Pyridin-4-yl)amino]ethan-1-olHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 22624908HCID 22624908, compoundYield 79.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Diethyl azodicarboxylate (261 mg, 1.5 mmol) was added dropwise to a suspension of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (160 mg, 0.5 mmol), (prepared as described for the starting material in Example 24), triphenylphosphine (393 mg, 1.5 mmol) and 2-(N-(4-pyridyl)amino)ethanol (97 mg, 0.7 mmol) in methylene chloride (8 ml) and the mixture stirred for 2 hours at ambient temperature. The mixture was diluted with ethyl acetate (5 ml), the solid product was collected by filtration and purified by chromatography on an aluminium oxide column eluting with methylene chloride/acetonitrile/methanol (60/35/5). The purified solid was triturated with ether and collected by filtration. The solid was dissolved in a mixture of methylene chloride/methanol and 3M ethereal hydrogen chloride (0.5 ml) was added. The volatiles were removed by evaporation, the solid residue was suspended in ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-(4-pyridyl)amino)ethoxy)quinazoline hydrochloride (95 mg, 37%). 1H NMR Spectrum: (DMSOd6; CF3COOD) 3.87(t, 2H); 4.00(s, 3H); 4.43(t, 2H); 6.97(dd, 1H); 7.15(dd, 1H); 7.43(s, 1H); 7.46(dd, 1H); 7.66(t, 1H); 7.68(dd, 1H); 8.12(d, 1H); 8.21(s, 1H); 8.34(d, 1H); 8.89(s, 1H) MS-ESI: 440 [MH]+

Workup

  1. custom(prepared
  2. filtrationthe solid product was collected by filtration
  3. custompurified by chromatography on an aluminium oxide column
  4. washeluting with methylene chloride/acetonitrile/methanol (60/35/5)
  5. customThe purified solid was triturated with ether
  6. filtrationcollected by filtration
  7. dissolutionThe solid was dissolved in a mixture of methylene chloride/methanol and 3M ethereal hydrogen chloride (0.5 ml)
  8. additionwas added
  9. customThe volatiles were removed by evaporation
  10. filtrationcollected by filtration
  11. washwashed with ether
  12. customdried under vacuum

Sources & evidence

ORD record
ord-e07aca24d5064b42b00a98cb587b8780
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

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