Methanesulfonic Acid → 1-[N-cyclohexylcarbonyl-N-(2-pyridyl)-2-aminoethyl]-4-(2,5-dichlorobenzyl)pipe-razine methanesulfonate hemihydrate

HRID 649813Notes

Reaction equation

HRID 649813 reaction equation
[CH:1]([CH2:3][N:4]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1)[C:5]([CH:7]1[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1)=[O:6])=[O:2].[Cl:19][C:20]1[CH:32]=[CH:31][C:30]([Cl:33])=[CH:29][C:21]=1[CH2:22][N:23]1[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]1.C([BH3-])#N.[Na+].[CH3:38][S:39]([OH:42])(=[O:41])=[O:40]>C(OCC)(=O)C.CO>[OH2:2].[CH3:38][S:39]([OH:42])(=[O:41])=[O:40].[CH:7]1([C:5]([N:4]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[CH2:3][CH2:1][N:26]2[CH2:25][CH2:24][N:23]([CH2:22][C:21]3[CH:29]=[C:30]([Cl:33])[CH:31]=[CH:32][C:20]=3[Cl:19])[CH2:28][CH2:27]2)=[O:6])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.[CH:7]1([C:5]([N:4]([CH2:3][CH2:1][N:26]2[CH2:25][CH2:24][N:23]([CH2:22][C:21]3[CH:29]=[C:30]([Cl:33])[CH:31]=[CH:32][C:20]=3[Cl:19])[CH2:28][CH2:27]2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)=[O:6])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.[CH3:38][S:39]([OH:42])(=[O:41])=[O:40]

Participants

7

Reactant 4

HCID 6395Methanesulfonic AcidHCID 46433681-[(2,5-Dichlorophenyl)methyl]piperazineHCID 5003444Sodium cyanoborohydrideHCID 21713921N-Formylmethyl-N-(2-pyridyl)cyclohexanecarboxamide

Product 1

HCID 1317228271-[N-cyclohexylcarbonyl-N-(2-pyridyl)-2-aminoethyl]-4-(2,5-dichlorobenzyl)pipe-razine methanesulfonate hemihydrateYield 19%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture comprising 0.164 g of Compound 1B of Example 1, 0.210 g of Compound 14B, and 4 mL methanol, continuously stirred under nitrogen, at room temperature, there was added 0.049 g of sodium cyanoborohydride. The resulting mixture was then stirred for 13 hr, at room temperature, followed by dilution with 10 mL water, and subsequent extraction with ethyl acetate (3×10 mL). The collected organic phases were then dried over anhydrous sodium sulphate, followed by vacuum evaporation, and subsequent purification of the obtained product residue by flash chromatography (chloroform—methanol 95:5). The solvents were then evaporated off, from the recovered fractions, yielding a residual substance which was then solubilized into 2 mL ethyl acetate. To this solution was then added 0.08 mL methanesulphonic acid (2 M solution of CH3SO3H, in ethanol) followed by diethyl ether, until the complete precipitation of the product. 0.071 g of this end-product precipitate was recovered here (yield 19%), through the use of vacuum filtration procedures.

Workup

  1. extractionfollowed by dilution with 10 mL water, and subsequent extraction with ethyl acetate (3×10 mL)
  2. dry with materialThe collected organic phases were then dried over anhydrous sodium sulphate
  3. customfollowed by vacuum evaporation, and subsequent purification of the obtained product residue by flash chromatography (chloroform—methanol 95:5)
  4. customThe solvents were then evaporated off, from the recovered fractions
  5. customyielding a residual substance which
  6. customfollowed by diethyl ether, until the complete precipitation of the product
  7. custom0.071 g of this end-product precipitate was recovered here (yield 19%)
  8. filtrationthrough the use of vacuum filtration procedures

Sources & evidence

ORD record
ord-ca4ffdb01c214f0cbe0979a3b3e7a341
Source dataset
uspto-grants-2001_08
Patent number
US06271234B1

Reaction notes

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