Triphenylphosphine → 7-((2-Chloro-6-methyl-4-pyridyl)methoxy)-4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-6-methoxyquinazoline

HRID 1384586Notes

Reaction equation

HRID 1384586 reaction equation
N(C(OCC)=O)=NC(OCC)=O.Cl.[F:14][C:15]1[CH:34]=[C:33]([CH3:35])[C:32]([O:36][C:37]([O:39][CH3:40])=[O:38])=[CH:31][C:16]=1[NH:17][C:18]1[C:27]2[C:22](=[CH:23][C:24]([OH:30])=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:60][C:61]1[CH:66]=[C:65]([CH2:67]O)[CH:64]=[C:63]([CH3:69])[N:62]=1>C(Cl)Cl>[Cl:60][C:61]1[CH:66]=[C:65]([CH2:67][O:30][C:24]2[CH:23]=[C:22]3[C:27]([C:18]([NH:17][C:16]4[CH:31]=[C:32]([O:36][C:37]([O:39][CH3:40])=[O:38])[C:33]([CH3:35])=[CH:34][C:15]=4[F:14])=[N:19][CH:20]=[N:21]3)=[CH:26][C:25]=2[O:28][CH3:29])[CH:64]=[C:63]([CH3:69])[N:62]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 22504306(2-Chloro-6-methylpyridin-4-yl)methanolHCID 1356711794-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride

Product 1

HCID 226249947-((2-Chloro-6-methyl-4-pyridyl)methoxy)-4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-6-methoxyquinazolineYield 78%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (296 μl, 1.88 mmol) was added dropwise to a solution of 4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride (350 mg, 0.94 mmol), (prepared as described for the starting material in Example 22), triphenylphosphine (492 mg, 1.88 mmol) and 2-chloro-4-hydroxymethyl-6-methylpyridine (178 mg, 1.12 mmol) in methylene chloride (30 ml) and the mixture stirred for 30 minutes at ambient temperature. The solvent was removed by evaporation and the residue was purified by column chromatography eluting with ethyl acetate/methylene chloride (75/25). The purified product was triturated with ether, the solid collected by filtration, washed with ether and dried under vacuum to give 7-((2-chloro-6-methyl-4-pyridyl)methoxy)-4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-6-methoxyquinazoline (373 mg, 78%). 1H NMR Spectrum: (DMSOd6) 2.15(s, 3H); 2.5(s, 3H); 3.85(s, 3H); 3.98(s, 3H); 5.35(s, 2H) 7.25(s, 1H); 7.3(d, 1H); 7.35(s, 1H); 7.4(m, 2H); 7.85(s, 1H); 8.35(s, 1H); 9.58(1H) MS-ESI: 513 [MH]+

Workup

  1. custom(prepared
  2. customThe solvent was removed by evaporation
  3. customthe residue was purified by column chromatography
  4. washeluting with ethyl acetate/methylene chloride (75/25)
  5. customThe purified product was triturated with ether
  6. filtrationthe solid collected by filtration
  7. washwashed with ether
  8. customdried under vacuum

Sources & evidence

ORD record
ord-50efb0d9e8a344d8814b1867f0dbad50
Source dataset
uspto-grants-2001_07
Patent number
US06258951B1

Reaction notes

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