Tributylphosphine → HCID 18753431, compound

HRID 1838569Notes

Reaction equation

HRID 1838569 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.[O:41]1[CH2:45][CH2:44][CH:43]([CH2:46]O)[CH2:42]1.C(P(CCCC)CCCC)CCC>C(Cl)Cl.CCOCC>[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][CH2:46][CH:43]4[CH2:44][CH2:45][O:41][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 139980Tetrahydro-3-furanmethanolHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 18753431HCID 18753431, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

1,1′-(Azodicarbonyl)dipiperidine (560 mg, 2.2 mmol) was added in portions to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (240 mg, 0.75 mmol), (prepared as described for the starting material in Example 2), tetrahydro-3-furanmethanol (90 mg, 0.88 mmol) and tributylphosphine (440 mg, 2.2 mmol) in methylene chloride (12 ml) and the mixture stirred for 18 hours. The mixture was diluted with ether, and the resulting precipitate was removed by filtration. The solvent was removed from the filtrate by evaporation, and the residue was dissolved in acetone and ethereal hydrogen chloride (0.75 ml of a 1M solution, 0.75 mmol) was added. The mixture was diluted with ether and the resulting precipitate was collected by filtration. The solid was purified by column chromatography eluting with methylene chloride/acetonitrile/methanol (a gradient from 50150/1 to 50/5012). The purified product was triturated with ether, collected by filtration and dried to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(tetrahydrofuran-3-ylmethoxy)quinazoline (93 mg, 31%).

Workup

  1. custom(prepared
  2. customthe resulting precipitate was removed by filtration
  3. customThe solvent was removed from the filtrate by evaporation
  4. dissolutionthe residue was dissolved in acetone
  5. additionethereal hydrogen chloride (0.75 ml of a 1M solution, 0.75 mmol) was added
  6. additionThe mixture was diluted with ether
  7. filtrationthe resulting precipitate was collected by filtration
  8. customThe solid was purified by column chromatography
  9. washeluting with methylene chloride/acetonitrile/methanol (a gradient from 50150/1 to 50/5012)
  10. customThe purified product was triturated with ether
  11. filtrationcollected by filtration
  12. customdried

Sources & evidence

ORD record
ord-e402dd60abfa49408026069f49629519
Source dataset
uspto-grants-2004_01
Patent number
US06673803B2

Reaction notes

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