Acetic Acid → HCID 22624939, compound

HRID 279552Notes

Reaction equation

HRID 279552 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.C(P(CCCC)CCCC)CCC.O[CH2:55][CH2:56][CH2:57][C:58]1[CH:63]=[CH:62][N:61]=[CH:60][CH:59]=1.C(O)(=O)C>C(Cl)Cl>[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][CH2:55][CH2:56][CH2:57][C:58]4[CH:63]=[CH:62][N:61]=[CH:60][CH:59]=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 5

HCID 176Acetic AcidHCID 13831TributylphosphineHCID 729234-PyridinepropanolHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 22624939HCID 22624939, compoundYield 156.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1,1′-(Azodicarbonyl)dipiperidine (1.06 g, 4.2 mmol) in methylene chloride (15 ml) was added dropwise to a solution of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (448 mg, 1.4 mmol), (prepared as described for the starting material in Example 24), tributylphosphine (848 mg, 4.2 mmol) and 4-(3-hydroxypropyl)pyridine (322 mg, 2.4 mmol) in methylene chloride (15 ml) and the mixture stirred for 3 hours at ambient remperature. Acetic acid (126 mg, 2.1 mmol) was added and the solvent was removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5). The purified product was triturated with ether, the resulting solid collected and dissolved in methylene chloride (20 ml). 5M Hydrogen chloride in isopropanol solution (0.7 ml) was added, the solution was diluted with isopropanol (5 ml) and concentrated by evaporation to a total volume of 4 ml. Ether was added and the resulting soild was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(3-(4-pyridyl)propoxy)quinazoline hydrochloride (520 mg, 73%).

Workup

  1. custom(prepared
  2. customthe solvent was removed by evaporation
  3. customThe residue was purified by column chromatography
  4. washeluting with methylene chloride/methanol (95/5)
  5. customThe purified product was triturated with ether
  6. customthe resulting solid collected
  7. dissolutiondissolved in methylene chloride (20 ml)
  8. addition5M Hydrogen chloride in isopropanol solution (0.7 ml) was added
  9. additionthe solution was diluted with isopropanol (5 ml)
  10. concentrationconcentrated by evaporation to a total volume of 4 ml
  11. additionEther was added
  12. filtrationthe resulting soild was collected by filtration
  13. washwashed with ether
  14. customdried under vacuum

Sources & evidence

ORD record
ord-e061bb20f3134b5fa8d4aaebd2d6fde5
Source dataset
uspto-grants-2002_03
Patent number
US06362336B1

Reaction notes

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