Triphenylphosphine → HCID 21701586, compound

HRID 1596285Notes

Reaction equation

HRID 1596285 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][O:55][CH2:56][CH2:57][CH2:58]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][CH2:58][CH2:57][CH2:56][O:55][CH3:54])=[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 11776TriphenylphosphineHCID 741163-Methoxy-1-propanolHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 21701586HCID 21701586, compoundYield 58.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Diethyl azodicarboxylate (123 μl, 0.88 mmol) was added portionwise to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (250 mg, 0.8 mmol), (prepared as described for the starting material in Example 4), triphenylphosphine (228 mg, 0.96 mmol) and 3-methoxy-1-propanol (71 mg, 0.8 mmol) in methylene chloride (20 ml) cooled at 0° C. The mixture was then allowed to warn to ambient temperature and stirred for 18 hours. The resulting precipitate was removed by filtration and the solvent removed from the filtrate by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol/concentrated aqueous ammonia (100/8/1). The purified oil was treated with ethereal hydrogen chloride and the volatiles were then removed by evaporation. The residue was triturated with ether and the solid collected by filtration to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-methoxypropoxy)quinazoline hydrochloride (100 mg, 32%) as a yellow solid.

Workup

  1. custom(prepared
  2. customto warn to ambient temperature
  3. customThe resulting precipitate was removed by filtration
  4. customthe solvent removed from the filtrate by evaporation
  5. customThe residue was purified by column chromatography
  6. washeluting with methylene chloride/methanol/concentrated aqueous ammonia (100/8/1)
  7. additionThe purified oil was treated with ethereal hydrogen chloride
  8. customthe volatiles were then removed by evaporation
  9. customThe residue was triturated with ether
  10. filtrationthe solid collected by filtration

Sources & evidence

ORD record
ord-0090259c4d0a43988cf4edcaf0f18f82
Source dataset
uspto-grants-2001_09
Patent number
US06291455B1

Reaction notes

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