Triphenylphosphine → HCID 18753419, compound

HRID 547229Notes

Reaction equation

HRID 547229 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.O[CH2:55][CH2:56][N:57]1[C:62](=[O:63])[CH2:61][O:60][CH2:59][C:58]1=[O:64]>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][CH2:56][N:57]4[C:62](=[O:63])[CH2:61][O:60][CH2:59][C:58]4=[O:64])=[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 220568ethyl N-ethoxycarbonyliminocarbamateHCID 18753439HCID 18753439, compoundHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 18753419HCID 18753419, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Diethyl azodicarboxylate (472 μl, 3 mmol) was added dropwise to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (319.5 mg, 1 mmol), (prepared as described for the staring material in Example 2), triphenylphosphine (786 mg, 3 mmol) and 4-(2-hydroxyethyl)-3,5-dioxomorpholine (223 mg, 1.4 mmol) in methylene chloride (10 ml) under nitrogen. The mixture was stirred at ambient temperature for 4.5 hours and the insolubles were removed by filtration. The solvent was removed from the filtrate by evaporation and the residue was purified by column chromatography eluting with methylene chloride/acetonitrile/methanol (85/12.5/2.5). The purified product was dissolved in methylene chloride, 2M ethereal hydrogen chloride (1 ml) was added and the mixture was diluted with ether. The resulting precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-7-(2-(3,5-dioxomorpholino)ethoxy)-6-methoxyquinazoline hydrochloride (97 mg, 20%).

Workup

  1. custom(prepared
  2. customthe insolubles were removed by filtration
  3. customThe solvent was removed from the filtrate by evaporation
  4. customthe residue was purified by column chromatography
  5. washeluting with methylene chloride/acetonitrile/methanol (85/12.5/2.5)
  6. dissolutionThe purified product was dissolved in methylene chloride
  7. addition2M ethereal hydrogen chloride (1 ml) was added
  8. additionthe mixture was diluted with ether
  9. filtrationThe resulting precipitate was collected by filtration
  10. washwashed with ether
  11. customdried under vacuum

Sources & evidence

ORD record
ord-2344d92324fa4b09aafd383eecc8e00a
Source dataset
uspto-grants-2011_05
Patent number
USRE042353E1

Reaction notes

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