Hydrochloric Acid → HCID 118661229, compound

HRID 64044Notes

Reaction equation

HRID 64044 reaction equation
[CH3:1][N:2]([CH3:24])[C:3]([C@@H:5]1[CH2:10][C@@H:9]([NH:11][S:12]([NH:15][C:16](=[O:22])[O:17][C:18]([CH3:21])([CH3:20])[CH3:19])(=[O:14])=[O:13])[C@H:8]([OH:23])[CH2:7][CH2:6]1)=[O:4].[CH3:25][S:26](Cl)(=[O:28])=[O:27].CN1CCOCC1.Cl>C(#N)C.O>[CH3:25][S:26]([O:23][C@@H:8]1[CH2:7][CH2:6][C@H:5]([C:3](=[O:4])[N:2]([CH3:1])[CH3:24])[CH2:10][C@H:9]1[NH:11][S:12](=[O:13])(=[O:14])[NH:15][C:16]([O:17][C:18]([CH3:20])([CH3:21])[CH3:19])=[O:22])(=[O:28])=[O:27]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 79724-MethylmorpholineHCID 31297Methanesulfonyl chlorideHCID 118671017Edoxaban Impurity 158

Product 1

HCID 118661229HCID 118661229, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6342AcetonitrileSolvent2×

Conditions

Temperature
0 °C

Procedure

Acetonitrile (30 ml) was added to a solution of tert-butyl {[(1R,2R,5S)-5-(dimethylcarbamoyl)-2-hydroxycyclohexyl]sulfamoyl}carbamate (12.1 g) in acetonitrile (30 ml), and the obtained solution was then cooled to approximately 0° C. Thereafter, methanesulfonyl chloride (3.77 ml) was added to the reaction solution. N-methylmorpholine (6.81 ml) was added dropwise to the reaction mixture, and the obtained mixture was then stirred for approximately 3 hours. Thereafter, water (61 ml) was added to the reaction mixture, and a 6 mol/l hydrochloric acid solution was then added thereto to adjust the pH of the mixture to pH 3. Water (93 ml) was further added to the mixture, and the thus obtained mixture was then stirred for approximately 15 hours. Thereafter, the precipitated solid was collected by filtration and was then washed with a 27.5% acetonitrile aqueous solution (30 ml). The obtained solid was dried under reduced pressure to obtain the title compound (13.0 g, yield: 89%). The spectra of the resulting product, which were obtained using various devices, were matched with those obtained in Example 5.

Workup

  1. stirringthe thus obtained mixture was then stirred for approximately 15 hours
  2. filtrationThereafter, the precipitated solid was collected by filtration
  3. washwas then washed with a 27.5% acetonitrile aqueous solution (30 ml)
  4. customThe obtained solid was dried under reduced pressure

Sources & evidence

ORD record
ord-1fb1f05ad3bf4e20b81263a886db0439
Source dataset
uspto-grants-2016_09
Patent number
US09447118B2

Reaction notes

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