Dimethylformamide → HCID 54290276, compound
Reaction equation
[C:1]([O:18][CH2:19][C@H:20]1[O:24][C@@H:23]([N:25]2[CH:32]=[CH:31][C:29]([NH2:30])=[N:28][C:26]2=[O:27])[C@@H:22]([OH:33])[C@@H:21]1[OH:34])(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16].CN(C)C=O.[C:40]([O:44][C:45]([NH:47][CH2:48][C:49]([NH:51][CH2:52][C:53]([NH:55][C@H:56]([C:64](O)=[O:65])[CH2:57][C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)=[O:54])=[O:50])=[O:46])([CH3:43])([CH3:42])[CH3:41].C1(N=C=NC2CCCCC2)CCCCC1>CCOCC.O1CCOCC1>[C:1]([O:18][CH2:19][C@H:20]1[O:24][C@@H:23]([N:25]2[CH:32]=[CH:31][C:29]([NH:30][C:64](=[O:65])[C@H:56]([CH2:57][C:58]3[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=3)[NH:55][C:53](=[O:54])[CH2:52][NH:51][C:49](=[O:50])[CH2:48][NH:47][C:45]([O:44][C:40]([CH3:42])([CH3:41])[CH3:43])=[O:46])=[N:28][C:26]2=[O:27])[C@@H:22]([OH:33])[C@@H:21]1[OH:34])(=[O:17])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH3:16]Participants
Conditions
- Temperature
- 5 °C
Procedure
A solution consisting of 4.82 g. (0.01 mole) 1-(5'-O-palmitoyl-β-D-arabinofuranosyl)cytosine and a solvent mixture consisting of equal parts dimethylformamide and dioxane was obtained by warming slightly. This solution was cooled to 5° C. and 3.8 g. (0.01 mole) N-[N-[N-(tertbutoxycarbonyl)glycyl]glycyl]-L-phenylalanine was added, followed by 2.47 g. (0.012 mole) dicyclohexylcarbodiimide. This reaction mixture was stirred continuously for 4 days while the temperature was maintained at 5° C. The reaction mixture was then filtered in order to remove the dicyclohexylurea that had formed. The solvents were removed from the filtrate by evaporation under reduced pressure. The residual oil thus obtained was dissolved in 25 ml. diethyl ether, and the ether solution was set aside in a refrigerator for about 16 hrs. Some solids that separated were removed by filtering, and the filtrate was concentrated to a glass by removing the ether by evaporation. The glassy residue was dissolved in 50 ml. of a solvent system consisting of 72 parts methyl ethyl ketone, 20 parts acetone, and 8 parts water, and the solution was poured onto a column of silica gel 45 mm. × 115 cm. amounting to 800 g. which had been equilibrated with this same solvent. The chromatogram was developed with about 100 ml. of the solvent mixture, and then 10 ml. fractions were collected. After combining fractions 75 through 105, and concentrating the solution by evaporation of the solvents under reduced pressure, the concentrate was lyophilized. There was thus obtained 4.0 g. of 1-(5'-O-palmitoyl-β-D-arabinofuranosyl)-N4 -[N-[N-[N-(tert-butoxycarbonyl)glycyl]glycyl]-L-phenylalanyl]cytosine having optical rotation [α]D25 = +46° (c 1.1 in methanol)
Workup
- temperatureby warming slightly
- temperaturewas maintained at 5° C
- filtrationThe reaction mixture was then filtered in order
- customto remove the dicyclohexylurea that
- customhad formed
- customThe solvents were removed from the filtrate by evaporation under reduced pressure
- customThe residual oil thus obtained
- dissolutionwas dissolved in 25 ml
- customSome solids that separated
- customwere removed
- filtrationby filtering
- concentrationthe filtrate was concentrated to a glass
- customby removing the ether
- customby evaporation
- dissolutionThe glassy residue was dissolved in 50 ml
- additionthe solution was poured onto a column of silica gel 45 mm
- customfractions were collected
- concentrationconcentrating the solution
- customby evaporation of the solvents under reduced pressure
Sources & evidence
- ORD record
- ord-3873e98a29a34f49ba504646f0c2c5fd
- Source dataset
- uspto-grants-1976_08
- Patent number
- US03975367
Reaction notes
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