Triphenylphosphine → HCID 22478228, compound

HRID 1838564Notes

Reaction equation

HRID 1838564 reaction equation
N(C(OCC)=O)=NC(OCC)=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:32][C:33]1[CH:52]=[CH:51][C:36]([NH:37][C:38]2[C:47]3[C:42](=[CH:43][C:44]([OH:50])=[C:45]([O:48][CH3:49])[CH:46]=3)[N:41]=[CH:40][N:39]=2)=[C:35]([F:53])[CH:34]=1.[C:54]([O:58][C:59]([NH:61][CH2:62][CH2:63]O)=[O:60])([CH3:57])([CH3:56])[CH3:55]>C(Cl)Cl>[C:54]([O:58][C:59]([NH:61][CH2:62][CH2:63][O:50][C:44]1[CH:43]=[C:42]2[C:47]([C:38]([NH:37][C:36]3[CH:51]=[CH:52][C:33]([Cl:32])=[CH:34][C:35]=3[F:53])=[N:39][CH:40]=[N:41]2)=[CH:46][C:45]=1[O:48][CH3:49])=[O:60])([CH3:57])([CH3:56])[CH3:55]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 2733206tert-butyl N-(2-hydroxyethyl)carbamateHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 22478228HCID 22478228, compoundYield 25.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Diethyl azodicarboxylate (0.94 ml, 6 mmol) was added dropwise to a mixture of triphenylphosphine (1.57 g, 6 mmol), 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (640 mg, 2 mmol), (prepared as described for the starting material in Example 2), and N-(tert-butoxycarbonyl)ethanolamine (0.354 g, 2.2 mmol) in methylene chloride (20 ml) at 0° C. The reaction mixture was allowed to warm to ambient temperature and stirred for 4 hours. The reaction mixture was diluted with methylene chloride, washed with aqueous sodium hydrogen carbonate solution, water and then brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol/aqueous ammonia (100/8/1). The product was recrystallised from acetonitrile, collected by filtration, washed with ethyl acetate and dried to give 7-(2-[N-tert-butoxycarbonylamino]ethoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (235 mg,25%).

Workup

  1. custom(prepared
  2. customat 0° C
  3. washwashed with aqueous sodium hydrogen carbonate solution, water
  4. dry with materialbrine, dried (MgSO4)
  5. customthe solvent removed by evaporation
  6. customThe residue was purified by column chromatography
  7. washeluting with methylene chloride/methanol/aqueous ammonia (100/8/1)
  8. customThe product was recrystallised from acetonitrile
  9. filtrationcollected by filtration
  10. washwashed with ethyl acetate
  11. customdried

Sources & evidence

ORD record
ord-98e8121026544581bf007f36e5072c8c
Source dataset
uspto-grants-2004_01
Patent number
US06673803B2

Reaction notes

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