Dimethylcarbamoyl Chloride → HCID 18396082, compound

HRID 843030Notes

Reaction equation

HRID 843030 reaction equation
Cl.Cl.[NH:3]1[CH2:8][CH2:7][NH:6][CH2:5][C@@H:4]1[C:9]([OH:11])=[O:10].[CH3:12][N:13]([CH3:17])[C:14](Cl)=[O:15].[S:18](Cl)(=[O:21])(=[O:20])N.[F:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]2[CH2:31][CH2:32][NH:33][CH2:34][CH:35]=2)=[CH:26][CH:25]=1>C[Si](C)(C)N[Si](C)(C)C.C(#N)C>[CH3:12][N:13]([CH3:17])[C:14]([N:6]1[CH2:7][CH2:8][N:3]([S:18]([CH:34]2[CH2:35][C:30]([C:27]3[CH:26]=[CH:25][C:24]([F:23])=[CH:29][CH:28]=3)=[CH:31][CH2:32][NH:33]2)(=[O:21])=[O:20])[C@@H:4]([C:9]([OH:11])=[O:10])[CH2:5]1)=[O:15]

Participants

6

Reactant 3

HCID 6598Dimethylcarbamoyl ChlorideHCID 12680090(2R)-Piperazine-2-carboxylic acid--hydrogen chloride (1/2)HCID 86754904HCID 86754904, compound

Product 1

HCID 18396082HCID 18396082, compoundYield 70.7%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 13838HexamethyldisilazaneSolvent

Conditions

Temperature
120 °C

Procedure

Piperazine-2(R)-carboxylic acid dihydrochloride (5.0 g, 24.6 mmol) was suspended in hexamethyldisilazane (50 ml). The reaction mixture was heated at about 120° C. to achieve complete dissolution and then cooled to about 80° C. A solution of dimethylcarbamoyl chloride (3.18 g, 29.5 mmol) in acetonitrile (5 ml) was added and the reaction mixture is stirred overnight at about 80° C. A solution of 4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine sulfamoyl chloride (5.4 g, 19.58 mmol) in acetonitrile (10 ml) was added and the resulting reaction mixture was stirred at about 80° C. till the completion of the reaction (followed by HPLC). The reaction mixture was cooled and then quenched with methanol. The resulting slurry was concentrated and then replaced into water. The aqueous slurry was made alkaline with ammonium hydroxide and then washed with dichloromethane. The aqueous phase was acidified with dilute HCl and extracted with dichoromethane. The organic extracts were washed with water and then evaporated to dryness to yield 4-(N,N-dimethylaminocarbonyl)-1-[4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridinesulfonyl]piperazine-2 (R)-carboxylic acid (6.1 g) as a beige colored solid.

Workup

  1. dissolutiondissolution
  2. temperaturecooled to about 80° C
  3. customthe resulting reaction mixture
  4. stirringwas stirred at about 80° C. till the completion of the reaction (followed by HPLC)
  5. temperatureThe reaction mixture was cooled
  6. customquenched with methanol
  7. concentrationThe resulting slurry was concentrated
  8. washwashed with dichloromethane
  9. extractionextracted with dichoromethane
  10. washThe organic extracts were washed with water
  11. customevaporated to dryness

Sources & evidence

ORD record
ord-d33e76bf3e904f60903b90de831be97c
Source dataset
uspto-grants-2002_04
Patent number
US06376506B1

Reaction notes

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