Tributylphosphine → HCID 22624977, compound

HRID 1737517Notes

Reaction equation

HRID 1737517 reaction equation
N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[ClH:19].[F:20][C:21]1[CH:40]=[C:39](C)[C:38]([O:42][C:43]([O:45][CH3:46])=[O:44])=[CH:37][C:22]=1[NH:23][C:24]1[C:33]2[C:28](=[CH:29][C:30]([OH:36])=[C:31]([O:34][CH3:35])[CH:32]=2)[N:27]=[CH:26][N:25]=1.C(P(CCCC)CCCC)CCC.O[CH2:61][CH2:62][CH2:63][C:64]1[CH:69]=[CH:68][N:67]=[CH:66][CH:65]=1>C(Cl)Cl>[Cl:19][C:39]1[C:38]([O:42][C:43]([O:45][CH3:46])=[O:44])=[CH:37][C:22]([NH:23][C:24]2[C:33]3[C:28](=[CH:29][C:30]([O:36][CH2:61][CH2:62][CH2:63][C:64]4[CH:69]=[CH:68][N:67]=[CH:66][CH:65]=4)=[C:31]([O:34][CH3:35])[CH:32]=3)[N:27]=[CH:26][N:25]=2)=[C:21]([F:20])[CH:40]=1

Participants

6

Reactant 4

HCID 13831TributylphosphineHCID 729234-PyridinepropanolHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 1356711794-(2-Fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride

Product 1

HCID 22624977HCID 22624977, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

1,1'-(Azodicarbonyl)dipiperidine (2.52 g, 10 mmol) in methylene chloride (10 ml) was added dropwise to a solution of 4-(2-fluoro-5-methoxycarbonyloxy-4-methylanilino)-7-hydroxy-6-methoxyquinazoline hydrochloride (1.38 g, 3.5 mmol), (prepared as described for the starting material in Example 22), tributylphosphine (2 g, 10.5 mmol) and 4-(3-hydroxypropyl)pyridine (720 mg, 5.25 mmol) in methylene chloride (25 ml) and the mixture stirred for 2.5 hours at ambient temperature. The solvent was removed by evaporation and the residue was triturated with petroleum ether. The solid product was collected by filtration and purified by column chromatography eluting with methylene chloride/methanol (95/5) to give 4-(4-chloro-2-fluoro-5-methoxycarbonyloxyanilino)-6-methoxy-7-(3-(4-pyridyl)propoxy)quinazoline (1.2 g, 67%).

Workup

  1. custom(prepared
  2. customThe solvent was removed by evaporation
  3. customthe residue was triturated with petroleum ether
  4. filtrationThe solid product was collected by filtration
  5. custompurified by column chromatography
  6. washeluting with methylene chloride/methanol (95/5)

Sources & evidence

ORD record
ord-65a48fac3bc64017831e5a5596b732f1
Source dataset
uspto-grants-1999_10
Patent number
US05962458

Reaction notes

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