Tributylphosphine → 3-Chloro-4-fluorophenylamino-N-{2-methyl-5-[3-(4methylpiperazin-1yl)-propoxyl]phenyl}acetamide

HRID 1267924Notes

Reaction equation

HRID 1267924 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][CH2:10][C:11]([NH:13][C:14]2[CH:19]=[C:18]([OH:20])[CH:17]=[CH:16][C:15]=2[CH3:21])=[O:12])[CH:5]=[CH:6][C:7]=1[F:8].[CH3:22][N:23]1[CH2:28][CH2:27][N:26]([CH2:29][CH2:30][CH2:31]O)[CH2:25][CH2:24]1.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1.C(OCC)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][CH2:10][C:11]([NH:13][C:14]2[CH:19]=[C:18]([O:20][CH2:31][CH2:30][CH2:29][N:26]3[CH2:27][CH2:28][N:23]([CH3:22])[CH2:24][CH2:25]3)[CH:17]=[CH:16][C:15]=2[CH3:21])=[O:12])[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 4

HCID 13831TributylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 792083-(4-Methyl-1-piperazine)propan-1-olHCID 185423932-(3-chloro-4-fluoro-phenylamino)-N-(5-hydroxy-2-methyl-phenyl)-acetamide

Product 1

HCID 98037383-Chloro-4-fluorophenylamino-N-{2-methyl-5-[3-(4methylpiperazin-1yl)-propoxyl]phenyl}acetamideYield 57.4%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(3-chloro-4-fluoro-phenylamino)-N-(5-hydroxy-2-methyl-phenyl)-acetamide (0.400 g) and 4-methyl-1-piperazinepropanol (0.270 g) in tetrahydrofuran (20 ml) under a nitrogen atmosphere was added tributylphosphine (0.64 ml) and 1,1′-(azodicarbonyl)dipiperidine (0.656 g) and the mixture stirred at ambient temperature for 20 hours. The reaction mixture was poured into diethylether and filtered through Celite. After concentration, the residue was purified by NPHPLC (eluting with 75% ethanol in dichloromethane) to afford the title compound (0.334 g).

Workup

  1. filtrationfiltered through Celite
  2. concentrationAfter concentration
  3. customthe residue was purified by NPHPLC (eluting with 75% ethanol in dichloromethane)

Sources & evidence

ORD record
ord-69be2603638b43f9957102d23f707a93
Source dataset
uspto-grants-2003_04
Patent number
US06555541B1

Reaction notes

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