Glycol monoethyl ether → HCID 21701563, compound

HRID 1596286Notes

Reaction equation

HRID 1596286 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.[CH2:54]([O:56][CH2:57][CH2:58]O)[CH3:55]>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][CH2:55][CH2:54][O:56][CH2:57][CH3:58])=[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 8076Glycol monoethyl etherHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 21701563HCID 21701563, compoundYield 56%

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 2-ethoxyethanol (71 μl, 0.8 mmol) in methylene chloride (20 ml) cooled at 0° C. The mixture was then allowed to warm 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 chromatography eluting with methylene chloride/methanol (96/4). The resulting purified oil was dissolved in acetone and treated with water (80 μl) then ethereal hydrogen chloride. The resulting granular solid was collected by filtration to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-ethoxyethoxy)quinazoline hydrochloride (96 mg, 31%).

Workup

  1. custom(prepared
  2. temperatureto warm 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 chromatography
  6. washeluting with methylene chloride/methanol (96/4)
  7. customThe resulting purified oil
  8. dissolutionwas dissolved in acetone
  9. additiontreated with water (80 μl)
  10. filtrationThe resulting granular solid was collected by filtration

Sources & evidence

ORD record
ord-3e0b4224a2e04d8b82ebd579f361421c
Source dataset
uspto-grants-2001_09
Patent number
US06291455B1

Reaction notes

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