2-Methoxyethanol → HCID 21260358, compound

HRID 634656Notes

Reaction equation

HRID 634656 reaction equation
[C:1]([O:4][C:5]1[C:6]([Cl:26])=[CH:7][C:8]([F:25])=[C:9]([CH:24]=1)[NH:10][C:11]1[C:20]2[C:15](=[CH:16][C:17]([OH:23])=[C:18]([O:21][CH3:22])[CH:19]=2)[N:14]=[CH:13][N:12]=1)(=[O:3])[CH3:2].[CH3:27][O:28][CH2:29][CH2:30]O.C(P(CCCC)CCCC)CCC>C(Cl)Cl>[C:1]([O:4][C:5]1[C:6]([Cl:26])=[CH:7][C:8]([F:25])=[C:9]([CH:24]=1)[NH:10][C:11]1[C:20]2[C:15](=[CH:16][C:17]([O:23][CH2:30][CH2:29][O:28][CH3:27])=[C:18]([O:21][CH3:22])[CH:19]=2)[N:14]=[CH:13][N:12]=1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 80192-MethoxyethanolHCID 13831TributylphosphineHCID 135549381HCID 135549381, compound

Product 1

HCID 21260358HCID 21260358, compoundYield 62.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

1-1′-(Azodicarbonyl)dipiperidine (413 mg, 1.6 mmol) was added portionwise to a stirred mixture of 4-(5-acetoxy-4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (250 mg, 0.66 mmol), 2-methoxyethanol (63 ml, 0.8 mmol) and tributylphosphine (405 ml, 1.6 mmol) in methylene chloride at 0° C. The resulting solution was allowed to warm to ambient temperature and stirred for 2 hours. The precipitated solid was removed by filtration, the solvent removed from the filtrate by evaporation and the residue purified by flash chromatography eluting with acetonitrile/methylene chloride (1/9 increasing in polarity to 4/6) to give 4-(5-acetoxy4-chloro-2-fluoroanilino)-6-methoxy-7-(2-methoxyethoxy)quinazoline (180 mg, 62%) as a solid.

Workup

  1. customThe precipitated solid was removed by filtration
  2. customthe solvent removed from the filtrate by evaporation
  3. customthe residue purified by flash chromatography
  4. washeluting with acetonitrile/methylene chloride (1/9 increasing in polarity to 4/6)

Sources & evidence

ORD record
ord-e656b062c56d41128ec8d03a24463334
Source dataset
uspto-grants-2001_02
Patent number
US06184225B2

Reaction notes

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