4-Methylmorpholine → 3-(4'-Chlorobiphenyl-4-yl)propynoic acid-[4-(4-methylpiperazin-1-ylmethyl)phenyl]amide

HRID 735043Notes

Reaction equation

HRID 735043 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]#[C:15][C:16]([OH:18])=O)=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[CH3:34][N:35]1[CH2:40][CH2:39][N:38]([CH2:41][C:42]2[CH:47]=[CH:46][C:45]([NH2:48])=[CH:44][CH:43]=2)[CH2:37][CH2:36]1>C1COCC1>[CH3:34][N:35]1[CH2:40][CH2:39][N:38]([CH2:41][C:42]2[CH:47]=[CH:46][C:45]([NH:48][C:16](=[O:18])[C:15]#[C:14][C:11]3[CH:10]=[CH:9][C:8]([C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=4)=[CH:13][CH:12]=3)=[CH:44][CH:43]=2)[CH2:37][CH2:36]1

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 31539964-((4-Methylpiperazin-1-yl)methyl)anilineHCID 68816492(4'-Chlorobiphenyl-4-yl)propynoic acid

Product 1

HCID 578457233-(4'-Chlorobiphenyl-4-yl)propynoic acid-[4-(4-methylpiperazin-1-ylmethyl)phenyl]amide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 0.26 g (1 mmol) of (4′-chlorobiphenyl-4-yl)propynoic acid and 0.12 mL (1.1 mmol) of N-methylmorpholine in 20 mL of absolute THF is combined at −15° C. with 0.14 mL (1.1 mmol) of isobutyl chloroformate and stirred for ten minutes. Then 0.226 g (1.1 mmol) of 4-(4-methylpiperazin-1-ylmethyl)phenylamine dissolved in 7 mL of THF is added and the reaction mixture is stirred for 2 hours until ambient temperature is reached. The reaction mixture is evaporated down and the residue is dissolved in dichloromethane. The organic phase is washed twice with water and then dried over sodium sulfate. The desiccant is filtered off and the solvent is distilled off. The residue is triturated with ether and suction filtered. The purification is carried out by column chromatography on silica gel (dichloromethane/methanol/ammonia (90/10/0.1)). Yield: 60 mg (14% of theory); melting point: 182° C.-185° C.; C27H26ClN3O (M=443.97); calc.: molecular ion peak (M+H)+: 444/446 (Cl); found: molecular ion peak (M+H)+: 444/446 (Cl); Rf value: 0.4 (silica gel, dichloromethane/methanolic ammonia (90:10:0.1)).

Workup

  1. additionis added
  2. stirringthe reaction mixture is stirred for 2 hours until ambient temperature
  3. customThe reaction mixture is evaporated down
  4. dissolutionthe residue is dissolved in dichloromethane
  5. washThe organic phase is washed twice with water
  6. dry with materialdried over sodium sulfate
  7. filtrationThe desiccant is filtered off
  8. distillationthe solvent is distilled off
  9. customThe residue is triturated with ether and suction
  10. filtrationfiltered
  11. customThe purification

Sources & evidence

ORD record
ord-1eae23011e644a289f62901cefc36a47
Source dataset
uspto-grants-2009_09
Patent number
US07592373B2

Reaction notes

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