Triphenylphosphine → HCID 5329030, compound

HRID 547216Notes

Reaction equation

HRID 547216 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.O[CH:36]1[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(Cl)Cl>[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][CH:36]4[CH2:41][CH2:40][N:39]([CH3:42])[CH2:38][CH2:37]4)=[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 660484-Piperidinol, 1-methyl-HCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 5329030HCID 5329030, compoundYield 86.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

Diethyl azodicarboxylate (218 mg, 1.25 mmol) was added dropwise to a solution of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (159 mg, 0.5 mmol), (prepared as described for the starting material in Example 2), 4-hydroxy-1-methylpiperidine (115 mg, 1 mmol) and triphenylphosphine (328 mg, 1.25mmol) in methylene chloride (5 ml) cooled at 5° C. under nitrogen. The mixture was stirred for 1 hour at ambient temperature, the solvent was removed by evaporation and the residue was partitioned between 2M hydrochloric acid and ether. The aqueous layer was separated, adjusted to pH9 with aqueous sodium hydrogen carbonate solution and extracted with methylene chloride. The methylene chloride layer was washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified on neutral alumina eluting with methylene chloride/methanol (97/3). The purified product was triturated with ether, collected by filtration and dried to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(1-methylpiperidine-4-yloxy)quinazoline (180 mg, 79%).

Workup

  1. custom(prepared
  2. customthe solvent was removed by evaporation
  3. customthe residue was partitioned between 2M hydrochloric acid and ether
  4. customThe aqueous layer was separated
  5. extractionextracted with methylene chloride
  6. washThe methylene chloride layer was washed with brine
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed by evaporation
  9. customThe residue was purified on neutral alumina eluting with methylene chloride/methanol (97/3)
  10. customThe purified product was triturated with ether
  11. filtrationcollected by filtration
  12. customdried

Sources & evidence

ORD record
ord-791829bad06e49fba5fb3adf7ba29a64
Source dataset
uspto-grants-2011_05
Patent number
USRE042353E1

Reaction notes

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