4-Methylmorpholine → HCID 18175216, compound

HRID 395960Notes

Reaction equation

HRID 395960 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([NH:12][C:13]1[N:21]=[C:20]2[C:16]([C:17]([C:29]3[CH:34]=[CH:33][N:32]=[CH:31][CH:30]=3)=[C:18]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[NH:19]2)=[CH:15][CH:14]=1)=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:36]([O:38][CH2:39][CH:40]([CH3:42])[CH3:41])=[O:37].CN1CCOCC1.C(=O)([O-])[O-].[K+].[K+]>O.CN(C=O)C>[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]([NH:12][C:13]1[N:21]=[C:20]2[C:16]([C:17]([C:29]3[CH:30]=[CH:31][N:32]=[CH:33][CH:34]=3)=[C:18]([C:22]3[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=3)[N:19]2[C:36]([O:38][CH2:39][CH:40]([CH3:42])[CH3:41])=[O:37])=[CH:15][CH:14]=1)=[O:11])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 11430Potassium CarbonateHCID 62365Isobutyl chloroformateHCID 12968338HCID 12968338, compound

Product 1

HCID 18175216HCID 18175216, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

6-(2′-t-butoxycarbonylamino-1′-oxo-ethylamino)-3-(4-pyridyl)-2-(4-fluorophenyl)-7-aza-indole (29) (50 mg, 0.108 mmol), isobutyl chloroformate (42 ml, 0.325 mmol), N-methylmorpholine (119 ml, 1.08 mmol), potassium carbonate (74.9 mg, 0.542 mmol), and DMF (4 mL) were warmed at 80° C. for 16 h. After cooling to 23 C., the reaction was diluted with water (20 mL), extracted with ethyl acetate (2×20 mL), and dried (Na2SO4). After concentration in vacuo, the residue was purified by preparative plate chromatography to afford 6-(2′-t-butoxycarbonylamino-1′-oxo-ethylamino)-3-(4-pyridyl)-2-(4-fluorophenyl)-1-isobutoxycarbonyl-7-aza-indole (142). Compound (104) was converted to 6-(2′-amino-1′-oxo-ethylamino)-3-(4-pyridyl)-2-(4-fluorophenyl)-1-isobutoxycarbonyl-7-aza-indole (143) in the manner of example 6: Mass Spectrum (CI) 462 (MH+).

Workup

  1. temperatureAfter cooling to 23 C
  2. extractionextracted with ethyl acetate (2×20 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationAfter concentration in vacuo
  5. customthe residue was purified by preparative plate chromatography

Sources & evidence

ORD record
ord-8875ca5e2a284f43951940b0eaa59730
Source dataset
uspto-grants-2003_08
Patent number
US06605634B2

Reaction notes

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