Acetamide, N-(trimethylsilyl)- → HCID 86587226, compound

HRID 2414694Notes

Reaction equation

HRID 2414694 reaction equation
C(OC([N:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24]([NH:26][CH2:27][C@H:28]([NH:32][C:33](=[O:36])[CH2:34][NH2:35])[C:29]([OH:31])=[O:30])=[O:25])[CH2:19]2)=[O:17])[CH2:10][CH2:9]1)=O)(C)(C)C.C[Si](C)(C)NC(=O)C.[Cl-].[CH3:46][O:47][C:48](=[O:58])[C:49]1[CH:57]=[CH:56][C:52]([C:53]([OH:55])=O)=[CH:51][CH:50]=1.S([O-])(O)(=O)=O.[K+]>C(#N)C>[NH:8]1[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24]([NH:26][CH2:27][C@H:28]([NH:32][C:33](=[O:36])[CH2:34][NH:35][C:53](=[O:55])[C:52]3[CH:51]=[CH:50][C:49]([C:48]([O:47][CH3:46])=[O:58])=[CH:57][CH:56]=3)[C:29]([OH:31])=[O:30])=[O:25])[CH2:19]2)=[O:17])[CH2:10][CH2:9]1

Participants

6

Reactant 4

HCID 25989Acetamide, N-(trimethylsilyl)-HCID 516920Potassium bisulfateHCID 53442854Terephthalic acid monomethylester chlorideHCID 86587227HCID 86587227, compound

Product 1

HCID 86587226HCID 86587226, compoundYield 80.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a stirred solution of N-[(3R)-1-{3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl}-3-piperidylcarbonyl]-2(S)-(2-aminoacetyl)amino-β-alanine (600 mg) and N-trimethylsilylacetoamide (770 mg) in acetonitrile (10 mL) was added terephtalic acid monomethyl ester chloride (233 mg) at 4° C. After stirring for 3 hours, the reaction mixture was acidified with 5% aqueous potassium hydrogensulfate solution and extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate. The organic layer was evaporated and the residue was treated with 4 N—HCl in ethyl acetate. The resulting insoluble material was collected by filtration, dried and dissolved in water. The solution was neutralized with an aqueous saturated sodium hydrogencarbonate solution, purified by ODS column chromatography (Daisogel-120sp®) eluting with 5, 10, 15 and 20% CH3CN/H2O and lyophilized to give N-[(3R)-1-{3-(4-piperidyl)propionyl}-3-piperidylcarbonyl]-2(S)-(2-((4-methoxycarbonylbenzoyl)amino)acetyl)amino-β-alanine (500.5 mg, 74.6%) as an amorphous powder.

Workup

  1. extractionextracted with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customThe organic layer was evaporated
  5. additionthe residue was treated with 4 N—HCl in ethyl acetate
  6. filtrationThe resulting insoluble material was collected by filtration
  7. customdried
  8. dissolutiondissolved in water
  9. custompurified by ODS column chromatography (Daisogel-120sp®)
  10. washeluting with 5, 10, 15 and 20% CH3CN/H2O

Sources & evidence

ORD record
ord-ef08bc107d2f42c48b2fa2b2bab2602f
Source dataset
uspto-grants-2004_11
Patent number
US06812235B2

Reaction notes

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