Dicyclohexylcarbodiimide → HCID 178448382, compound

HRID 1169554Notes

Reaction equation

HRID 1169554 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

Conditions

Temperature
0 °C

Procedure

A mixture 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 5 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. stirringstirred for 18 hrs
  2. filtrationfiltered
  3. customThe solvent of the filtrate was partially removed in vacuo
  4. additionthe impure solution was added dropwise to cold diethyl ether
  5. filtrationThe resulting precipitate (2) was filtered
  6. customdried
  7. 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-def81f503ff74d67990aadde8e8e6be9
Source dataset
uspto-grants-2010_11
Patent number
US07825086B2

Reaction notes

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