Triphenylphosphine → 4-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-6-methoxy-7-(2-(4-pyridyl)ethoxy)quinazoline

HRID 279558Notes

Reaction equation

HRID 279558 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.[N:60]1[CH:65]=[CH:64][C:63]([CH2:66][CH2:67]O)=[CH:62][CH:61]=1>C(Cl)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]([O:30][CH2:67][CH2:66][C:63]3[CH:64]=[CH:65][N:60]=[CH:61][CH:62]=3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 729214-PyridineethanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1356711794-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride

Product 1

HCID 226250584-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-6-methoxy-7-(2-(4-pyridyl)ethoxy)quinazolineYield 90%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (244 mg, 1.4 mmol) was added to a suspension of 4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride (261 mg, 0.7 mmol), (prepared as described for the starting material in Example 22), triphenylphosphine (367 mg, 1.4 mmol) and 2-(4-pyridyl)ethanol (104 mg, 0.84 mmol), (Zhur. Obshchei. Khim. 1958, 28, 103-110), in methylene chloride and the mixture stirred for 30 minutes at ambient temperature. The solvent was removed by evaporation. The residue was suspended in ether and the ether then decanted. The resulting crude oil was purified by column chromatography eluting with methylene chloride/methanol (90/10) to give 4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-6-methoxy-7-(2-(4-pyridyl)ethoxy)quinazoline (300 mg, 90%).

Workup

  1. custom(prepared
  2. customThe solvent was removed by evaporation
  3. customthe ether then decanted
  4. customThe resulting crude oil was purified by column chromatography
  5. washeluting with methylene chloride/methanol (90/10)

Sources & evidence

ORD record
ord-45e4a98f6e4949ac81b1b0e19cd125ef
Source dataset
uspto-grants-2002_03
Patent number
US06362336B1

Reaction notes

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