4-Methylmorpholine → HCID 18791574, compound

HRID 1005595Notes

Reaction equation

HRID 1005595 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:49]=[CH:48][CH:47]=[CH:46][C:14]=1[C:15]([NH:17][C:18]1[CH:43]=[CH:42][C:21]([C:22]([N:24]([CH3:41])[C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][C:26]=2[O:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][C:38](O)=[O:39])=[O:23])=[CH:20][C:19]=1[O:44][CH3:45])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(Cl)(=O)C(C)(C)C.[NH2:64][N:65]1[CH2:70][CH2:69][N:68]([CH3:71])[CH2:67][CH2:66]1.C(=O)([O-])O.[Na+]>ClCCl>[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:49]=[CH:48][CH:47]=[CH:46][C:14]=1[C:15]([NH:17][C:18]1[CH:43]=[CH:42][C:21]([C:22]([N:24]([CH3:41])[C:25]2[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][C:26]=2[O:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][C:38]([NH:64][N:65]2[CH2:70][CH2:69][N:68]([CH3:71])[CH2:67][CH2:66]2)=[O:39])=[O:23])=[CH:20][C:19]=1[O:44][CH3:45])=[O:16])=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

7

Reactant 5

HCID 79724-MethylmorpholineHCID 62493Pivaloyl chlorideHCID 813491-Amino-4-methylpiperazineHCID 516892Sodium BicarbonateHCID 18791200HCID 18791200, compound

Product 1

HCID 18791574HCID 18791574, compoundYield 72.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-[2-(3-tert-butoxycarbonylaminoprop-1-yl)oxybenzoyl]amino-3-methoxy-N-methyl-N-[2-(5-carboxypent-1-yl)oxy-4-methylphenyl]benzamide (250 mg) and N-methylmorpholine (37 mg) in dichloromethane (5 ml) was added pivaloyl chloride (45 mg) at -15° C. After being stirred at the same temperature for 5 minutes, to the mixture was added 1-amino-4-methylpiperazine (47 mg) and the mixture was stirred at -15° C. for 1 hour and then stirred at ambient temperature for additional 2 hours. The resulting mixture was poured into saturated aqueous sodium hydrogen carbonate solution (20 ml) and the solution was extracted with chloroform (15 ml×3). The organic layer was washed with brine and dried over magnesium sulfate. The solvent was evaporated and the residue was purified on silica gel column chromatography (SiO3 30 g, 1-15% methanol in chloroform) to give 4-[2-(3-tert-butoxycarbonylaminoprop-1-yl)oxybenzoyl]amino-3-methoxy-N-methyl-N-[2-[5-(4-methylpiperazine-1-yl)aminocarbonylpent-1-yl]oxy-4-methylphenyl]benzamide (208 mg).

Workup

  1. stirringthe mixture was stirred at -15° C. for 1 hour
  2. stirringstirred at ambient temperature for additional 2 hours
  3. extractionthe solution was extracted with chloroform (15 ml×3)
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customThe solvent was evaporated
  7. customthe residue was purified on silica gel column chromatography (SiO3 30 g, 1-15% methanol in chloroform)

Sources & evidence

ORD record
ord-f7e4c68f0a43484d956b8857b3d91073
Source dataset
uspto-grants-2000_04
Patent number
US06054457

Reaction notes

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