Tributylphosphine → HCID 4913175, compound

HRID 1596270Notes

Reaction equation

HRID 1596270 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([CH3:10])[CH2:6][CH2:5]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>[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[CH2:9][CH2:8][N:7]([CH3:10])[CH2:6][CH2:5]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

6

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 2311841-(2-Hydroxyethyl)-4-methylpiperazineHCID 1355137204-(4-Chloro-2-fluorophenylamino)-7-hydroxy-6-methoxyquinazoline

Product 1

HCID 4913175HCID 4913175, compoundYield 25.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1-(2-hydroxyethyl)4-methylpiperazine (112 mg, 0.78 mmol) in methylene chloride (1 ml) was added to a stirred suspension of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxy-quinazoline (225 mg, 0.7 mmol), (prepared as described for the starting material in Example 4), and tributylphosphine (420 mg, 2.1 mmol) in methylene chloride (10 ml). 1,1′-(Azodicarbonyl)dipiperidine (525 mg, 2.1 mmol) was then added in portions to the mixture. The resulting clear, pale yellow solution was stirred for 3.5 hours, then allowed to stand overnight. The reaction mixture was quenched with ether (8 ml) and the precipitate was removed by filtration. The solvent was removed from the filtrate by evaporation and the residue dissolved in acetone and treated with 1M ethereal hydrogen chloride until the hydrochloride salt precipitated. The precipitate was collected by filtration, dissolved in methanol and then basified with excess triethylamine. The volatiles were removed by evaporation and the residue purified by column chromatography eluting with methylene chloride/methanol/0.88 aqueous ammonia (100/8/1). The resulting purified oil was triturated with ether, collected by filtration and dried to give 4-(4-chloro-2-fluoroanilino)-6-methoxy 7-(2-(4-methylpiperazin-1-yl)ethoxy)quinazoline (79 mg, 25%) as a white solid.

Workup

  1. custom(prepared
  2. waitto stand overnight
  3. customThe reaction mixture was quenched with ether (8 ml)
  4. customthe precipitate was removed by filtration
  5. customThe solvent was removed from the filtrate by evaporation
  6. dissolutionthe residue dissolved in acetone
  7. additiontreated with 1M ethereal hydrogen chloride until the hydrochloride salt
  8. customprecipitated
  9. filtrationThe precipitate was collected by filtration
  10. dissolutiondissolved in methanol
  11. customThe volatiles were removed by evaporation
  12. customthe residue purified by column chromatography
  13. washeluting with methylene chloride/methanol/0.88 aqueous ammonia (100/8/1)
  14. customThe resulting purified oil
  15. customwas triturated with ether
  16. filtrationcollected by filtration
  17. customdried

Sources & evidence

ORD record
ord-e8fe8d93d8264e7290c75210508331d1
Source dataset
uspto-grants-2001_09
Patent number
US06291455B1

Reaction notes

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