Tributylphosphine → HCID 18753456, compound

HRID 1838563Notes

Reaction equation

HRID 1838563 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.[CH:41]1([O:46][CH2:47][CH2:48]O)[CH2:45][CH2:44][CH2:43][CH2:42]1.C(P(CCCC)CCCC)CCC>C(Cl)Cl.CCOCC>[ClH:19].[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]([O:37][CH2:48][CH2:47][O:46][CH:41]4[CH2:45][CH2:44][CH2:43][CH2:42]4)=[C:32]([O:35][CH3:36])[CH:33]=3)[N:28]=[CH:27][N:26]=2)=[C:22]([F:40])[CH:21]=1

Participants

7

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 131875202-(Cyclopentyloxy)ethan-1-olHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 18753456HCID 18753456, compoundYield 118.1%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

1,1′-(Azodicarbonyl)dipiperidine (355 mg, 1.4 mmol) was added in portions to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (150 mg, 0.47 mmol), (prepared as described for the starting material in Example 2), 2-(cyclopentyloxy)ethanol (91 mg, 0.7 mmol), (U.S. Pat. No. 4,515,814), and tributylphosphine (284 mg, 1.4 mmol) in methylene chloride (6 ml) at 0° C. The mixture was then allowed to warm to ambient temperature and stirred for 3.5 hours. Ether (3 ml) was added and the insolubles were removed by filtration and the volatiles were removed from the filtrate by evaporation. The residue was dissolved in acetone and 1M ethereal hydrogen chloride (0.6 ml) was added. The mixture was left to stand for 60 hours and the precipitate was collected by filtration, washed with acetone and dried to give 4-(4-chloro-2-fluoroanilino)-7-(2-cyclopentyloxyethoxy)-6-methoxyquinazoline hydrochloride (130 mg, 60%).

Workup

  1. custom(prepared
  2. customat 0° C
  3. customthe insolubles were removed by filtration
  4. customthe volatiles were removed from the filtrate by evaporation
  5. dissolutionThe residue was dissolved in acetone
  6. addition1M ethereal hydrogen chloride (0.6 ml) was added
  7. waitThe mixture was left
  8. waitto stand for 60 hours
  9. filtrationthe precipitate was collected by filtration
  10. washwashed with acetone
  11. customdried

Sources & evidence

ORD record
ord-6a9816fa64364f1b80952f79367fcb11
Source dataset
uspto-grants-2004_01
Patent number
US06673803B2

Reaction notes

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