Dicyclohexylcarbodiimide → 2',3'-dideoxy-3'-fluoro-5'-O-{3-[1,3-bis-(N-CBZ-L-valyloxy)-2-propyloxycarbonyl]propanoyl} guanosine

HRID 1170673Notes

Reaction equation

HRID 1170673 reaction equation
[F:1][C@@H:2]1[C@@H:6]([CH2:7][OH:8])[O:5][C@@H:4]([N:9]2[C:19]3[N:18]=[C:16]([NH2:17])[NH:15][C:13](=[O:14])[C:12]=3[N:11]=[CH:10]2)[CH2:3]1.C1C=CC2N(O)N=NC=2C=1.[C:30]([NH:40][C@H:41]([C:45]([O:47][CH2:48][CH:49]([O:69][C:70](=[O:76])[CH2:71][CH2:72][C:73](O)=[O:74])[CH2:50][O:51][C:52](=[O:68])[C@H:53]([CH:65]([CH3:67])[CH3:66])[NH:54][C:55]([O:57][CH2:58][C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)=[O:56])=[O:46])[CH:42]([CH3:44])[CH3:43])([O:32][CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:31].C1CCC(N=C=NC2CCCCC2)CC1>CN(C1C=CN=CC=1)C.CN(C=O)C>[F:1][C@@H:2]1[C@@H:6]([CH2:7][O:8][C:73](=[O:74])[CH2:72][CH2:71][C:70]([O:69][CH:49]([CH2:50][O:51][C:52](=[O:68])[C@H:53]([CH:65]([CH3:67])[CH3:66])[NH:54][C:55]([O:57][CH2:58][C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=2)=[O:56])[CH2:48][O:47][C:45](=[O:46])[C@H:41]([CH:42]([CH3:44])[CH3:43])[NH:40][C:30]([O:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)=[O:31])=[O:76])[O:5][C@@H:4]([N:9]2[C:19]3[N:18]=[C:16]([NH2:17])[NH:15][C:13](=[O:14])[C:12]=3[N:11]=[CH:10]2)[CH2:3]1

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 23387471succinic acid 1,3-bis-(N-CBZ-L-valyloxy)-2-propyl esterHCID 1354318173'-Fluoro-2',3'-dideoxyguanosine

Product 1

HCID 1363351202',3'-dideoxy-3'-fluoro-5'-O-{3-[1,3-bis-(N-CBZ-L-valyloxy)-2-propyloxycarbonyl]propanoyl} guanosine

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2′,3′-dideoxy-3′-fluoroguanosine (17.8 g, 66 mmole), HOBT (10.64 g, 78.8 mmole), succinic acid 1,3-bis-(N-CBZ-L-valyloxy)-2-propyl ester (52 g, 78.8 mmole) and DMAP (0.96 g, 7.88 mmole) was coevaporated two times with DMF and reduced to about 500 ml. DCC (17.3 g, 84 mmole) was added and the mixture was stirred overnight at room temperature. The mixture was warmed for six hours at 60° C. and then cooled to about 110° C. The mixture was filtered and the solution was reduced under reduced pressure. 1200 ml of ethyl acetate was added and the organic phase was washed twice with 5% acetic acid, 5% sodium hydrogen carbonate and water. The organic phase was dried with sodium sulfate and evaporated under reduced pressure. The product was isolated by silica gel column chromatography. Yield: 42 g.

Workup

  1. temperatureThe mixture was warmed for six hours at 60° C.
  2. temperaturecooled to about 110° C
  3. filtrationThe mixture was filtered
  4. addition1200 ml of ethyl acetate was added
  5. washthe organic phase was washed twice with 5% acetic acid, 5% sodium hydrogen carbonate and water
  6. dry with materialThe organic phase was dried with sodium sulfate
  7. customevaporated under reduced pressure
  8. customThe product was isolated by silica gel column chromatography

Sources & evidence

ORD record
ord-a922354e194645eb9e5aa2aaccee36fb
Source dataset
uspto-grants-2010_11
Patent number
US07825238B2

Reaction notes

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