Tributylstannane → HCID 53848580, compound

HRID 1723263Notes

Reaction equation

HRID 1723263 reaction equation
C([SnH](CCCC)CCCC)CCC.[C:14]([NH:22][C:23]1[C:24]2[N:25]=[CH:26][N:27]([C:37]=2[N:38]=[CH:39][N:40]=1)[C@@H:28]1[O:36][C@H:33]([CH2:34][OH:35])[C@@H:31]([OH:32])[C@H:29]1[OH:30])(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.[C:41](Cl)([C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1)([C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1)[C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.C(Cl)(Cl)Cl>C1(C)C=CC=CC=1.O1CCCC1.N1C=CC=CC=1>[C:14]([NH:22][C:23]1[C:24]2[N:25]=[CH:26][N:27]([C:37]=2[N:38]=[CH:39][N:40]=1)[C@@H:28]1[O:36][C@H:33]([CH:34]([C:41]([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)([C:54]2[CH:55]=[CH:56][CH:57]=[CH:58][CH:59]=2)[C:48]2[CH:49]=[CH:50][CH:51]=[CH:52][CH:53]=2)[OH:35])[C@@H:31]([OH:32])[C@H:29]1[OH:30])(=[O:21])[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

8

Reactant 4

HCID 5948TributylstannaneHCID 6212ChloroformHCID 6456Trityl chlorideHCID 11728391N6-Benzoyladenosine

Product 1

HCID 53848580HCID 53848580, compound

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Compounds 3 and 9 are prepared treating N6 -benzoylated adenosine with monomethoxytrityl chloride in pyridine to yield the 5'-monomethoxytrityl derivative. The derivative is treated with t-butyldimethylsilylchloride in a mixture of pyridine and methylimidazole to form the N6 -benzoyl-2',3'-di-O-t-butyldimethylsilyl-5'-monomethoxytrityl adenosine. The trityl group is removed by acetic acid to produce compound 3. Compound 9 is synthesized analogously, starting with N6 -benzoylated tubercidin. This method of preparation is as described in Charubala et al, Liebigs Ann. Chem. 2392 (1981). Compound 4 is prepared by treating N6 -benzoylated-3'-deoxyadenosine with monomethoxytritylchloride to yield N6 -benzoyl-5'-O-monomethoxytrityl-3'-deoxyadenosine (cordycepin) which is converted to N6 -2'-O-dibenzoyl-3'-deoxyadenosine by benzoylation of the 2'-hydroxyl group with benzoylchloride followed by detritylation with 80% acetic acid for 30 minutes. This method of preparation is as described in Tetrahedron Lett. 21, 4077 (1980). Compound 5 is prepared by converting N6 -benzoyladenosine with t-butyldiphenylchlorosilane to the 5'-silylated nucleoside in pyridine. The 5'-silylated nucleoside is treated with triethyl orthoacetate followed by boron trifluoride/diethyl ether and sodium iodide in CH3CN (0° C., 1 hour) to yield the 3'-iodoacetyl derivative. The iodoacetyl derivative is converted to compound 5 by treatment with tributyltinhydride in toluene (80° C., 1 hour) and desilylation with ammonium tetrabutyl fluoride in tetrahydrofuran. This method of preparation is as described by Engles, J., in Tetrahedron Lett. 21, 4339 (1980), which is incorporated herein by reference. Compounds 6 and 7 are prepared by treating N6 -benzoyl adenosine with tritylchloride in pyridine and refluxing for 2 hours. N6 -benzoyl-5'-trityladenosine is isolated by extraction with chloroform. The water from the chloroform phase is removed by drying with sodium sulfate. N6 -benzoyl-2',5'-di-O-trityladenosine and N6 -benzoyl-3',5'-di-O-trityladenosine are isolated by preparative silica gel thin layer chromatography in chloroform/ethanol. Compounds 6 and 7 are prepared by treating the isolated compounds with n-pentylchloride and n-heptylchloride, respectively, under reflux in a suspension of sodium hydroxide in benzene. The solution is neutralized by refluxing in acetic acid followed by the addition of diethyl ether and water. The reaction products are extracted with chloroform followed by thin layer chromatography with chloroform:methanol (4:1) on silica gel plates. The trityl and benzoyl groups are removed by refluxing in acetic acid for one hour, cooling, extraction with diethyl ether, followed by concentration and cooling to yield crystalline compounds 6 and 7. This method of preparation is carried out according to Blank, H. U., Frahne, D., Myles, A. and Pfleiderer, W., Justus Liebigs Ann. Chem. 742, 34 (1970), which is incorporated herein by reference. Compound 8 was prepared as follows. 1 mmole of 3'-amino-3'-deoxyadenosine was reacted with 1.2 mmole of 1-methyl-3-nitrophenylethoxy carboxylimidazolium chloride in dimethylformamide, followed by the addition of hexamethyldisilazane to block the 2', 5' and 6-amino positions. 1.1 mmole of benzoyl chloride in pyridine was added at room temperature to produce blocked N6 -benzoyl-2',5'-disilyladenosine. The reaction mixture was poured into methanol-NH3 to remove the 2' and 5' silyl groups. Reaction with MMTr chloride in pyridine yielded the 5'-MMTr derivative. Tert-butyldimethylsilyl chloride in a mixture of pyridine and 1-methylimidazole was then added to the 5'-MMTr derivative and 5'-detritylated as in Example 1 to form compound 8.

Workup

  1. customThis method of preparation
  2. temperaturerefluxing for 2 hours

Sources & evidence

ORD record
ord-77f411ec9e8c4fa8ab5263a627f3f533
Source dataset
uspto-grants-1989_08
Patent number
US04859768

Reaction notes

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