N,N'-Dicyclohexylurea → (R)-9-[2(L-Valyloxymethyl)-4-(stearoyloxy)butyl]guanine

HRID 1369334

Reaction equation

HRID 1369334 reaction equation
C([NH:8][C@H:9]([C:13]([OH:15])=[O:14])[CH:10]([CH3:12])[CH3:11])(OC(C)(C)C)=O.C1(N=C=NC2CCCCC2)CCCCC1.C(NC1CCCCC1)(NC1CCCCC1)=O.O[CH2:48][C@H:49]([CH2:62][CH2:63][O:64][C:65](=[O:83])[CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH3:82])[CH2:50][N:51]1[CH:59]=[N:58][C:57]2[C:56](=[O:60])[NH:55][C:54]([NH2:61])=[N:53][C:52]1=2>ClCCl.CN(C)C1C=CN=CC=1.CN(C)C=O>[NH2:8][C@H:9]([C:13]([O:15][CH2:48][C@H:49]([CH2:62][CH2:63][O:64][C:65](=[O:83])[CH2:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH3:82])[CH2:50][N:51]1[CH:59]=[N:58][C:57]2[C:56](=[O:60])[NH:55][C:54]([NH2:61])=[N:53][C:52]1=2)=[O:14])[CH:10]([CH3:11])[CH3:12]

Participants

8

Reactant 4

HCID 4277N,N'-DicyclohexylureaHCID 10868DicyclohexylcarbodiimideHCID 83693Boc-L-ValineHCID 136343267(R)-9-[2-Hydroxymethyl-4-(stearoyloxy)butyl]guanine

Product 1

HCID 135423395(R)-9-[2(L-Valyloxymethyl)-4-(stearoyloxy)butyl]guanineYield 45.7%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of N-Boc-L-valine (528 mg; 2.1 mmol) and N,N′-dicyclohexyl carbodiimide (250 mg; 1.21 mmol) in dichloromethane (20 ml) was stirred over night at room temperature dicyclohexylurea filtered off and extracted with a small volume of dichloromethane, and the filtrate evaporated in vacuo to a small volume. (R)-9-[2-Hydroxymethyl-4-(stearoyloxy)butyl]guanine (340 mg; 0.654 mmol), 4-dimethylaminopyridine (25 mg; 0,205 mmol and dry N,N-dimethylformamide (15 ml) were added and the mixture was stirred for 4 h at 50° C. under N2. The solvent was evaporated in vacuo to a small volume. Column chromatography on silica gel, their on aluminum oxide (ethyl acetate:methanol: water 15:2:1 as eluent) gave 185 mg (39%) pure title compound as a white solid.

Workup

  1. filtrationfiltered off
  2. extractionextracted with a small volume of dichloromethane
  3. customthe filtrate evaporated in vacuo to a small volume
  4. customThe solvent was evaporated in vacuo to a small volume

Sources & evidence

ORD record
ord-d3660a85af1547cabea23c4b4d64dff1
Source dataset
uspto-grants-2003_06
Patent number
US06576763B1

Linked notes

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