Tributylphosphine → HCID 22625033, compound

HRID 279534Notes

Reaction equation

HRID 279534 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[CH:9]=[CH:8][C:7](=[O:10])[CH:6]=[CH:5]1.[Cl:11][C:12]1[CH:31]=[CH:30][C:15]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23](O)=[C:24]([O:27][CH3:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)=[C:14]([F:32])[CH:13]=1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C(Cl)Cl.CCOCC>[ClH:11].[Cl:11][C:12]1[CH:31]=[CH:30][C:15]([NH:16][C:17]2[C:26]3[C:21](=[CH:22][C:23]([O:1][CH2:2][CH2:3][N:4]4[CH:9]=[CH:8][C:7](=[O:10])[CH:6]=[CH:5]4)=[C:24]([O:27][CH3:28])[CH:25]=3)[N:20]=[CH:19][N:18]=2)=[C:14]([F:32])[CH:13]=1

Participants

7

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 22624935HCID 22624935, compoundHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 22625033HCID 22625033, compoundYield 32.3%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

1-(2-Hydroxyethyl)-1,4-dihydro-4-pyridone (221 mg, 1.6 mmol) was added to a stirred solution of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (230 mg, 0.7 mmol), (prepared as described for the starting material in Example 15), and tributylphosphine (0.53 ml, 2.1 mmol) in methylene chloride (20 ml) under nitrogen at 5° C. 1,1′-(Azodicarbonyl)dipiperidine (552 mg, 2.2 mmol) was added in portions over 10 minutes and the mixture was stirred at 5° C. for 2 hours, allowed to warm to ambient temperature and stirred for a further 18 hours. The mixture was diluted with ether, the insolubles removed by filtration and the solvent was removed from the filtrate by evaporation. The residue was partitioned between ethyl acetate and water, the organic phase was separated and dried (MgSO4), and solvent was removed by evaporation. The residue was dissolved in acetone and ethereal hydrogen chloride (1.2 ml of a 3M solution) was added. The mixture was left to stand for 15 minutes and the precipitated product was collected by filtration, washed with ether and dried to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-[2-(4-oxo-1,4-dihydro-1-pyridyl)ethoxy]quinazoline hydrochloride (54 mg, 16%).

Workup

  1. custom(prepared
  2. customat 5° C
  3. temperatureto warm to ambient temperature
  4. stirringstirred for a further 18 hours
  5. customthe insolubles removed by filtration
  6. customthe solvent was removed from the filtrate by evaporation
  7. customThe residue was partitioned between ethyl acetate and water
  8. customthe organic phase was separated
  9. dry with materialdried (MgSO4), and solvent
  10. customwas removed by evaporation
  11. dissolutionThe residue was dissolved in acetone
  12. additionethereal hydrogen chloride (1.2 ml of a 3M solution) was added
  13. waitThe mixture was left
  14. waitto stand for 15 minutes
  15. filtrationthe precipitated product was collected by filtration
  16. washwashed with ether
  17. customdried

Sources & evidence

ORD record
ord-4c3c5fd2d7cc41169ee71efdf7e5fbb1
Source dataset
uspto-grants-2002_03
Patent number
US06362336B1

Reaction notes

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