Tributylphosphine → 7-(3-Benzyloxypropoxy)4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride

HRID 279668

Reaction equation

HRID 279668 reaction equation
N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[Cl:19][C:20]1[CH:39]=[CH:38][C:23]([NH:24][C:25]2[C:34]3[C:29](=[CH:30][C:31]([OH:37])=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][N:26]=2)=[C:22]([F:40])[CH:21]=1.[CH2:41]([O:48][CH2:49][CH2:50][CH2:51]O)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.C(P(CCCC)CCCC)CCC>C(Cl)Cl.CCOCC>[ClH:19].[CH2:41]([O:48][CH2:49][CH2:50][CH2:51][O:37][C:31]1[CH:30]=[C:29]2[C:34]([C:25]([NH:24][C:23]3[CH:38]=[CH:39][C:20]([Cl:19])=[CH:21][C:22]=3[F:40])=[N:26][CH:27]=[N:28]2)=[CH:33][C:32]=1[O:35][CH3:36])[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1

Participants

7

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 3479713-Benzyloxy-1-propanolHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 226248927-(3-Benzyloxypropoxy)4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochlorideYield 56.6%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

1,1′-(azodicarbonyl)dipiperidine (480 mg, 1.9 mmol) was added in portions to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (200 mg, 0.63 mmol), 3-benzyloxypropanol (150 μl, 0.95 mmol) and tributylphosphine (459 μl, 1.86 mmol) in methylene chloride (20 ml) at 5° C. The reaction was stirred for 1 hour at 5° C. and then for 18 hours at ambient temperature. The mixture was diluted with ether and stirred for 15 minutes. The insolubles were removed by filtration and the volatiles were removed from the filtrate by evaporation. The residue was partitioned between ethyl acetate and water, and the organic layer was separated, dried (MgSO4) and the solvent removed by evaporation. A 1M solution of ethereal hydrogen chloride was added to the residue, the resulting solution was reduced in volume by evaporation and the resulting precipitate was collected by filtration and dried to give 7-(3-benzyloxypropoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (90 mg, 31%).

Workup

  1. waitfor 18 hours at ambient temperature
  2. stirringstirred for 15 minutes
  3. customThe insolubles were removed by filtration
  4. customthe volatiles were removed from the filtrate by evaporation
  5. customThe residue was partitioned between ethyl acetate and water
  6. customthe organic layer was separated
  7. dry with materialdried (MgSO4)
  8. customthe solvent removed by evaporation
  9. additionA 1M solution of ethereal hydrogen chloride was added to the residue
  10. customthe resulting solution was reduced in volume by evaporation
  11. filtrationthe resulting precipitate was collected by filtration
  12. customdried

Sources & evidence

ORD record
ord-375f564676b4499f817493dc5998a5e9
Source dataset
uspto-grants-2002_03
Patent number
US06362336B1

Linked notes

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