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Triphenylphosphine → 4-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-(4-pyridyl)ethoxy)quinazoline hydrochloride

HRID 1737523
Notes
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Reaction equation

HRID 1737523 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]([CH2:60][CH2:61]O)=[CH:56][CH:55]=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][CH2:61][CH2:60][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
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 729214-PyridineethanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 226250054-(4-Chloro-2-fluoroanilino)-6-methoxy-7-(2-(4-pyridyl)ethoxy)quinazoline hydrochlorideYield 54.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (315 μl, 2 mmol) was added dropwise to a solution of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (319.5 mg, 1 mmol), (prepared as described for the starting material in Example 24), triphenylphosphine (524 mg, 2 mmol) and 2-(4-pyridyl)ethanol (160 mg, 1.25 mmol), (Zhur. Obshchei. Khim. 1958, 28, 103-110), in methylene chloride (7 ml). The mixture was stirred for 1 hour at ambient temperature and the solvent was removed by evaporation. The residue was triturated with ether, the solid collected by filtration and purified by column chromatography eluting with methylene chloride/acetonitrile/methanol (85/10/5). The purified solid product was dissolved in a mixture of methylene chloride (50 ml) and methanol (50 ml) and 5M hydrochloric acid in isopropanol (0.5 ml) was added. After diluting with isopropanol (20 ml), the mixture was concentrated by evaporation. The precipitated solid was collected by filtration and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(4-pyridyl)ethoxy)quinazoline hydrochloride (125 mg, 25%).

Workup

  1. custom(prepared
  2. customthe solvent was removed by evaporation
  3. customThe residue was triturated with ether
  4. filtrationthe solid collected by filtration
  5. custompurified by column chromatography
  6. washeluting with methylene chloride/acetonitrile/methanol (85/10/5)
  7. dissolutionThe purified solid product was dissolved in a mixture of methylene chloride (50 ml) and methanol (50 ml) and 5M hydrochloric acid in isopropanol (0.5 ml)
  8. additionwas added
  9. additionAfter diluting with isopropanol (20 ml)
  10. concentrationthe mixture was concentrated by evaporation
  11. filtrationThe precipitated solid was collected by filtration
  12. customdried under vacuum

Sources & evidence

ORD record
ord-e9b2ecd37fac4b47abd246de9f8e0e20
Source dataset
uspto-grants-1999_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US05962458

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes