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

HRID 375165Notes

Reaction equation

HRID 375165 reaction equation
Cl.N[C@H](C)CSC1SC=C(C2C=CC=CC=2)N=1.SC1SC=C(C2C=CC=CC=2)N=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[S:87][CH:88]=[C:89]([C:91]4[CH:96]=[CH:95][CH:94]=[CH:93][CH:92]=4)[N:90]=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[S:87][CH:88]=[C:89]([C:91]3[CH:96]=[CH:95][CH:94]=[CH:93][CH:92]=3)[N:90]=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 228583042',3',5'-tri-O-acetyl-2-chloro-N-[(R)-1-(4-phenyl-2-thiazolyl)thio-2-propyl]adenosineHCID 677714532-[(R)-2-amino-1-propylthio]-4-phenylthiazole hydrochlorideHCID 1785278304-phenyl-1,3-thiazole-2-thiol

Product 1

HCID 228582792-chloro-N-[(R)-1-(4-phenyl-2-thiazolyl)thio-2-propyl]adenosineYield 20%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The title compound was prepared according to method A as described in Example 1 by reacting 2-[(R)-2-amino-1-propylthio]-4-phenylthiazole hydrochloride [prepared by a Mitsunobu reaction as described in Example 1 using 2-[(R)-N-tert-butyloxycarbonyl]amino-1-propanol (2.72 g, 15.5 mmol) and 2-mercapto-4-phenylthiazole (3.0 g, 15.5 mmol) followed by acidic hydrolysis] (1.15 g, 4.0 mmol) with 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (1.5 g, 3.35 mmol), followed by deacylation of the purified 2',3',5'-tri-O-acetyl-2-chloro-N-[(R)-1-(4-phenyl-2-thiazolyl)thio-2-propyl]adenosine using sodium methoxide in methanol to provide the title 2-chloro-N-[(R)-1-(4-phenyl- 2-thiazolyl)thio-2-propyl]adenosine (0.36 g, 20%) as a foam after column chromatography. 1H NMR (DMSO-d6) δ 1.37 (3H, d, --CHCH3), 3.4-3.73 (2H, m, 5'a and H-5'b and --CH2 --S--), 3.94 (1H, q, H-4), 4.13 (1H, q, H-3'), 4.52 (1H, q, H-2'), 4.71 (1H, m, --CHCH3), 5.06 (1H, t, 5'-OH), 5.22, 5.50 (2H, 2d, 2'- and 3'-OH), 5.83 (1H, d, H-1'), 7.33, 7.42 (3H, dt, Ar-H), 7.91 (2H, d, Ar-H), 8.41 (1H, s, H-2), 8.47 (1H, d, --NH). HPLC retention time 18.99 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-efe59a3e4e494052b76c1ad86a43409a
Source dataset
uspto-grants-1996_01
Patent number
US05484774

Reaction notes

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