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

HRID 990006
Notes
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Reaction equation

HRID 990006 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][CH:48]([CH2:58][O:59][C:60](=[O:76])[C@H:61]([CH:73]([CH3:75])[CH3:74])[NH:62][C:63]([O:65][CH2:66][C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1)=[O:64])[CH2:49][O:50][C:51](=[O:57])[CH2:52][CH2:53][C:54](O)=[O:55])=[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:54](=[O:55])[CH2:53][CH2:52][C:51]([O:50][CH2:49][CH: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:35]=[CH:36][CH:37]=[CH:38][CH:39]=2)=[O:31])[CH2:58][O:59][C:60](=[O:76])[C@H:61]([CH:73]([CH3:75])[CH3:74])[NH:62][C:63]([O:65][CH2:66][C:67]2[CH:68]=[CH:69][CH:70]=[CH:71][CH:72]=2)=[O:64])=[O:57])[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
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 68763170succinic acid 2,3-bis-(N-CBZ-L-valyloxy)-1-propyl esterHCID 1354318173'-Fluoro-2',3'-dideoxyguanosine

Product 1

HCID 1364003712',3'-dideoxy-3'-fluoro-5'-O-{3-[2,3-bis(N-CBZ-L-valyloxy)-1-propyloxycarbonyl]propanoyl}guanosine

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2′,3′dideoxy-3′-fluoroguanosine (0.538 g, 2 mmole), HOBT (0.327 g, 2.42 mmole), DMAP(29.3 mg, 0.24 mmole) and succinic acid 2,3-bis-(N-CBZ-L-valyloxy)-1-propyl ester (1.6 g, 2.42 mmole) was coevaporated two times with DMF and reduced to about 50 mL DCC (0.536 g, 2.6 mmole) was added and the mixture was stirred 72 hours at room temperature. The mixture was filtered and the solution was evaporated under reduced pressure. 100 ml of ethyl acetate was added and the organic phase 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: 0.65 g.

Workup

  1. additionwas added
  2. filtrationThe mixture was filtered
  3. customthe solution was evaporated under reduced pressure
  4. addition100 ml of ethyl acetate was added
  5. washthe organic phase 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-b1acf44f54534faeadec9df229f390b8
Source dataset
uspto-grants-2002_10
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06458772B1

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes