Cyclohexanone → HCID 71238639, compound

HRID 2175990Notes

Reaction equation

HRID 2175990 reaction equation
[C:1]([CH2:3][C:4]([NH:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][CH2:14][C:15]2[CH:24]=[CH:23][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:17][CH:16]=2)=[CH:9][CH:8]=1)=[O:5])#[N:2].[C:25]1(=O)[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.N1CCOCC1>C1(C)C=CC=CC=1>[C:1]([C:3](=[C:25]1[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1)[C:4]([NH:6][C:7]1[CH:8]=[CH:9][C:10]([CH2:13][CH2:14][C:15]2[CH:16]=[CH:17][C:18]([C:19]([O:21][CH3:22])=[O:20])=[CH:23][CH:24]=2)=[CH:11][CH:12]=1)=[O:5])#[N:2]

Participants

5

Reactant 3

HCID 7967CyclohexanoneHCID 8083MorpholineHCID 71238765HCID 71238765, compound

Product 1

HCID 71238639HCID 71238639, compound

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 54.0 g of methyl 4-(2-{4-[(cyanoacetyl)amino]phenyl}ethyl)benzoate, 50.0 mL of cyclohexanone, and 300 mL of toluene was added dropwise 15.0 mL of morpholine at room temperature. A Dean-Stark type dehydrating tube was attached to the reactor, and the reaction mixture was stirred for 3 hours with oil bath heated at 120° C. Thereafter, the reaction mixture was heated to reflux and further stirred for 1 hour. The reaction mixture was cooled to room temperature, followed by concentration under reduced pressure. 200 mL of diisopropylether was further added thereto, followed by stirring for 14 hours. The precipitated solid was collected by filtration, thereby obtaining 53.2 g of methyl 4-[2-(4-{[cyano(cyclohexylidene)acetyl]amino}phenyl)ethyl]benzoate. To a mixture of this solid, 4.5 g of sulfur and 80 mL of DMF was added dropwise 12.0 mL of morpholine at room temperature, and the reaction mixture was stirred for 1 hour at 50° C. Saturated brine was added to the reaction mixture, followed by extraction with ethyl acetate, and then the organic layer was washed with water and saturated brine. The organic layer was dried over anhydrous sodium sulfate, followed by filtration, and then the solvent was removed under reduced pressure. Isopropanol was added to the thus obtained residue, and the precipitated solid was collected by filtration, thereby obtaining 43.1 g of methyl 4-[2-(4-{[(2-amino-4,5,6,7-tetrahydro-1-benzothiophen-3-yl)carbonyl]amino}phenyl)ethyl]benzoate.

Workup

  1. temperatureThereafter, the reaction mixture was heated
  2. temperatureto reflux
  3. stirringfurther stirred for 1 hour
  4. temperatureThe reaction mixture was cooled to room temperature
  5. concentrationfollowed by concentration under reduced pressure
  6. addition200 mL of diisopropylether was further added
  7. stirringby stirring for 14 hours
  8. filtrationThe precipitated solid was collected by filtration

Sources & evidence

ORD record
ord-8ff68fd04b9c4beb8436334641340810
Source dataset
uspto-grants-2015_06
Patent number
US09062032B2

Reaction notes

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