Dicyclohexylcarbodiimide → HCID 178448382, compound

HRID 552079

Reaction equation

HRID 552079 reaction equation
[NH:1](C(OC(C)(C)C)=O)[C@H:2]([C:6]([OH:8])=[O:7])[CH:3]([CH3:5])[CH3:4].C1(N=C=NC2CCCCC2)CCCCC1.C1(N=C=NC2CCCCC2)CCCCC1.N(C(OC(C)(C)C)=O)[C@H](C(O)=O)C(C)C.[CH:61]1[N:65]([CH2:66][O:67][CH2:68][CH2:69]O)[C:64]2[N:71]=[C:72]([NH2:76])[N:73]=[C:74]([OH:75])[C:63]=2[N:62]=1>CN(C)C=O>[CH3:5][CH:3]([C@H:2]([NH2:1])[C:6]([O:8][CH2:69][CH2:68][O:67][CH2:66][N:65]1[C:64]2[NH:71][C:72]([NH2:76])=[N:73][C:74](=[O:75])[C:63]=2[N:62]=[CH:61]1)=[O:7])[CH3:4]

Participants

6

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 83693Boc-L-ValineHCID 131727499DCC Boc-ValHCID 178508933HCID 178508933, compound

Product 1

HCID 178448382HCID 178448382, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of the desired stereoisomeric form of Boc-Val, and dicyclohexyl carbodiimide (DCC), in dimethylformamide (DMF) in a ratio of 1:2 DCC/Boc-Val was stirred for 1 hr at 0° C. under nitrogen atmosphere. A solution of acyclovir (1) and 4-N,N(dimethylamino) pyridine (DMAP) was added to the reaction mixture, stirred for 18 hrs and then filtered. The solvent of the filtrate was partially removed in vacuo and the impure solution was added dropwise to cold diethyl ether. The resulting precipitate (2) was filtered and dried, followed by acidolytic removal (treating Boc-Val-ACV with trifluoroacetic acid (TFA) for 30 min at 0° C.) of the Boc protecting group to yield Val-ACV (3). Compound (3) was neutralized by triethylamine (TEA) and treated with the amino acid anhydride of Boc-Val for about hrs. The solvent was removed from the reaction mixture in vacuo and the reaction mixture was added dropwise to the cold diethyl ether. The resulting precipitate (4) was filtered, dried and the Boc group was deprotected (acidolytic removal) to yield the desired dipeptide ester of acyclovir Val-Val-ACV (5).

Workup

  1. filtrationfiltered
  2. customThe solvent of the filtrate was partially removed in vacuo
  3. additionthe impure solution was added dropwise to cold diethyl ether
  4. filtrationThe resulting precipitate (2) was filtered
  5. customdried
  6. customfollowed by acidolytic removal (treating Boc-Val-ACV with trifluoroacetic acid (TFA) for 30 min at 0° C.) of the Boc protecting group

Sources & evidence

ORD record
ord-1f5703a30f154dbfb206f4675e516fda
Source dataset
uspto-grants-2011_05
Patent number
US07951774B2

Linked notes

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