Acetic Acid → HCID 86584588, compound

HRID 1281622Notes

Reaction equation

HRID 1281622 reaction equation
CO[CH:3](OC)[CH2:4][C:5]1[CH:30]=[CH:29][C:8]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([S:16]([C:19]3[S:23][C:22]([NH:24][C:25](=[O:27])[CH3:26])=[N:21][C:20]=3[CH3:28])(=[O:18])=[O:17])[CH2:12][CH2:11]2)=[CH:7][CH:6]=1.[I-].[Na+].Cl[Si](Cl)(Cl)C.C(O)(=O)C.[NH2:44][CH2:45][C@@H:46]([C:48]1[CH:49]=[CH:50][C:51]([OH:59])=[C:52]([NH:54][S:55]([CH3:58])(=[O:57])=[O:56])[CH:53]=1)[OH:47].C([BH3-])#N.[Na+]>C(#N)C.CO.ClCCl>[OH:47][C@H:46]([C:48]1[CH:49]=[CH:50][C:51]([OH:59])=[C:52]([NH:54][S:55]([CH3:58])(=[O:57])=[O:56])[CH:53]=1)[CH2:45][NH:44][CH2:3][CH2:4][C:5]1[CH:6]=[CH:7][C:8]([NH:9][CH:10]2[CH2:15][CH2:14][N:13]([S:16]([C:19]3[S:23][C:22]([NH:24][C:25](=[O:27])[CH3:26])=[N:21][C:20]=3[CH3:28])(=[O:17])=[O:18])[CH2:12][CH2:11]2)=[CH:29][CH:30]=1

Participants

10

Reactant 6

HCID 176Acetic AcidHCID 5238Sodium IodideHCID 6399TrichloromethylsilaneHCID 5003444Sodium cyanoborohydrideHCID 12047933(R)-N-(5-(2-amino-1-hydroxyethyl)-2-hydroxyphenyl)methanesulfonamideHCID 18173818HCID 18173818, compound

Product 1

HCID 86584588HCID 86584588, compoundYield 7%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

N-[5-({4-[4-(2,2-dimethoxyethyl)anilino]-1-piperidinyl}sulfonyl)-4-methyl-1,3-thiazol-2-yl]acetamide (0.46 g, 0.953 mmol) was added to a pre-prepared mixture of sodium iodide (0.357 g, 2.38 mmol) and trichloro(methyl)silane (0.224 mL, 1.91 mmol) in anhydrous acetonitrile. The reaction was stirred at ambient temperature for 10 minutes. Dichloromethane was added and the reaction washed with 10% sodium thiosulfate solution, water and brine. The organic layer was dried over anhydrous magnesium sulfate, filtered and the solvent partially removed in vacuo. The aldehyde solution was used directly and treated with methanol, acetic acid (0.146 mL, 2.43 mmol), N-{5-[(1R)-2-amino-1-hydroxyethyl]-2-hydroxyphenyl}methanesulfonamide (0.235 g, 0.953 mmol) followed by sodium cyanoborohydride (0.06 g, 0.953 mmol). The reaction was stirred at ambient temperature for 24 hours. The reaction was taken to dryness in vacuo, adsorbed onto silica and purified by flash chromatography on silica gel Merck-60 (eluant: 5:1 chloroform-methanol containing 1% ammonium hydroxide) to yield the title compound (0.045 g, 0.067 mmol).

Workup

  1. washthe reaction washed with 10% sodium thiosulfate solution, water and brine
  2. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. customthe solvent partially removed in vacuo
  5. stirringThe reaction was stirred at ambient temperature for 24 hours
  6. custompurified by flash chromatography on silica gel Merck-60 (eluant: 5:1 chloroform-methanol containing 1% ammonium hydroxide)

Sources & evidence

ORD record
ord-aac110a54909488fb06244901c6ccfbf
Source dataset
uspto-grants-2002_09
Patent number
US06451814B1

Reaction notes

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