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

HRID 375166Notes

Reaction equation

HRID 375166 reaction equation
Cl.N[C@H](C)CSC1N=C(C2C=CC=CC=2)NN=1.SC1N=C(C2C=CC=CC=2)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:62][C@@H:63]1[C@H:67]([O:68]C(=O)C)[C@@H:66]([CH2:72][O:73]C(=O)C)[O:65][C@H:64]1[N:77]1[C:101]2[N:100]=[C:99]([Cl:102])[N:98]=[C:81]([NH:82][C@H:83]([CH3:97])[CH2:84][S:85][C:86]3[N:90]=[C:89]([C:91]4[CH:96]=[CH:95][CH:94]=[CH:93][CH:92]=4)[NH:88][N:87]=3)[C:80]=2[N:79]=[CH:78]1)(=O)C.C[O-].[Na+]>CO>[Cl:102][C:99]1[N:98]=[C:81]([NH:82][C@H:83]([CH3:97])[CH2:84][S:85][C:86]2[N:90]=[C:89]([C:91]3[CH:96]=[CH:95][CH:94]=[CH:93][CH:92]=3)[NH:88][N:87]=2)[C:80]2[N:79]=[CH:78][N:77]([C:101]=2[N:100]=1)[C@@H:64]1[O:65][C@H:66]([CH2:72][OH:73])[C@@H:67]([OH:68])[C@H:63]1[OH:62]

Participants

7

Reactant 5

HCID 102530272,6-Dichloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)purineHCID 10942334Sodium MethoxideHCID 22858306HCID 22858306, compoundHCID 22858328HCID 22858328, compoundHCID 178527978HCID 178527978, compound

Product 1

HCID 228583202-chloro-N-{(R)-1-[5-phenyl-(1,2,4-triazol-3-yl)]thio-2-propyl}adenosineYield 24%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The title compound was prepared according to method A as described in Example 1 by reacting 3-[(R)-2-amino-1-propylthio]-5-phenyl-1,2,4-triazole hydrochloride [prepared by a Mitsunobu reaction as described in Example 1 using 2-[(R)-N-tert-butyloxycarbonyl]amino-1-propanol (2.0 g, 11.4 mmol) and 3-mercapto-5-phenyl-1,2,4-triazole (2.0 g, 11 mmol) followed by acidic hydrolysis] (0.50 g, 1.8 mmol) with 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (0.75 g, 1.7 mmol), followed by deacylation of the purified 2',3',5'-tri-O-acetyl-2-chloro-N-{(R)-1-[5-phenyl-(1,2,4-triazol-3-yl)]thio-2-propyl}adenosine using sodium methoxide in methanol to provide the title 2-chloro-N-{(R)-1-[5-phenyl-(1,2,4-triazol-3-yl)]thio-2-propyl}adenosine (0.21 g, 24%) as a foam after column chromatography. 1H NMR (DMSO-d6)5 1.34 (3H, d, --CHCH3), 3.37-3.70 (4H, m, --CH2 --, H-5'a and H-5'b), 3.95 (1H, q, H-4), 4.13 (1H, t, H-3'), 4.53 (1H, t, H-2'), 4.59-4.69 (1H, m, --CHCH3), 5.07 (1H, t, 5'-OH), 5.22, 5.50 (2H, 2d, 2'- and 3'-OH), 5.83 (1H, d, H-1'), 7.43-7.54 (3H, m, Ar-H), 7.90, 8.0 (2H, m, Ar-H), 8.40 (1H, s, H-2). 8.42 (1H, d, --NH), HPLC retention time 14.5 min [gradient elution, 20-80% acetonitrile/water (containing 0.1% TFA)].

Workup

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

Sources & evidence

ORD record
ord-66e40d6c3a2440d3b16e10c805308402
Source dataset
uspto-grants-1996_01
Patent number
US05484774

Reaction notes

Loading…