2,6-Dichloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)purine → 2-chloro-N[(R)-1-(4-methyl-1,2,4-triazol-3-yl)thio-2-propyl]adenosine

HRID 375163

Reaktionsgleichung

Reaktionsgleichung von HRID 375163
Cl.N[C@H](C)CSC1N(C)C=NN=1.SC1N(C)C=NN=1.C(O[C@@H]1[C@H](OC(=O)C)[C@@H](COC(=O)C)O[C@H]1N1C=NC2C1=NC(Cl)=NC=2Cl)(=O)C.C([O:52][C@@H:53]1[C@H:57]([O:58]C(=O)C)[C@@H:56]([CH2:62][O:63]C(=O)C)[O:55][C@H:54]1[N:67]1[C:86]2[N:85]=[C:84]([Cl:87])[N:83]=[C:71]([NH:72][C@H:73]([CH3:82])[CH2:74][S:75][C:76]3[N:80]([CH3:81])[CH:79]=[N:78][N:77]=3)[C:70]=2[N:69]=[CH:68]1)(=O)C.C[O-].[Na+]>CO>[Cl:87][C:84]1[N:83]=[C:71]([NH:72][C@H:73]([CH3:82])[CH2:74][S:75][C:76]2[N:80]([CH3:81])[CH:79]=[N:78][N:77]=2)[C:70]2[N:69]=[CH:68][N:67]([C:86]=2[N:85]=1)[C@@H:54]1[O:55][C@H:56]([CH2:62][OH:63])[C@@H:57]([OH:58])[C@H:53]1[OH:52]

Komponenten

7

Edukt 5

HCID 102530272,6-Dichloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)purineHCID 10942334Sodium MethoxideHCID 228583032',3',5'-tri-O-acetyl-2-chloro-N-[(R)-1-(4-methyl-1,2,4-triazol-3-yl)thio-2-propyl]adenosineHCID 677717153-[(R)-2-amino-1-propylthio]-4-methyl-1,2,4-triazole hydrochlorideHCID 178481306HCID 178481306, Verbindung

Produkt 1

HCID 228582782-chloro-N[(R)-1-(4-methyl-1,2,4-triazol-3-yl)thio-2-propyl]adenosineAusbeute 17 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 887MethanolLösungsmittel

Versuchsvorschrift

The title compound was prepared according to method A as described in Example 1 by reacting 3-[(R)-2-amino-1-propylthio]-4-methyl-1,2,4-triazole hydrochloride [prepared by a Mitsunobu reaction as described in Example 1 using 2-[(R)-N-tert-butyloxycarbonyl]amino-1-propanol (3.5 g, 20 mmol) and 3-mercapto-4-methyl-1,2,4-triazole (2.3 g, 20 mmol) followed by acidic hydrolysis] (0.56 g, 2.2 mmol) with 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (1.0 g, 2.2 mmol), followed by deacylation of the purified 2',3',5'-tri-O-acetyl-2-chloro-N-[(R)-1-(4-methyl-1,2,4-triazol-3-yl)thio-2-propyl]adenosine using sodium methoxide in methanol to provide the title 2-chloro-N[(R)-1-(4-methyl-1,2,4-triazol-3-yl)thio-2-propyl]adenosine (0.17 g, 17%) as a foam after column chromatography. 1H NMR (DMSO-d6) δ 1.24 (3H, d, --CHCH3), 3.56, 3.67 (2H, ABX, 5'a and H-5'b), 3.95 (1H, q, H-4), 4.14 (1H, br q, H-3'), 4.15 -4.42 (2H, m, --CH2S--), 4.52 (1H, br q, H-2'), 4.80 (1H, m, --CHCH3), 5.07 (1H, br, 5'-OH), 5.22, 5.50 (2H, 2 br, 2'- and 3'-OH), 5.82 (1H, d, H-1'), 8.33 (1H, d,-NH), 8.39, 8.41 (2H, 2s, H-2 and Ar-H). HPLC retention time 7.79 min [gradient elution, 20-80% acetonitrile/water (containing 0.1% TFA)].

Aufarbeitung

  1. customThe title compound was prepared
  2. customprepared by a Mitsunobu reaction

Quellen und Nachweise

ORD-Eintrag
ord-941b3130e5bd4792a6eabddb604ee76b
Quelldatensatz
uspto-grants-1996_01
Patentnummer
US05484774

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