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

HRID 375161Notes

Reaction equation

HRID 375161 reaction equation
Cl.N[C@H](C)CSC1SC2C=CC(Cl)=CC=2N=1.ClC1C=CC2SC(S)=NC=2C=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:60][C@@H:61]1[C@H:65]([O:66]C(=O)C)[C@@H:64]([CH2:70][O:71]C(=O)C)[O:63][C@H:62]1[N:75]1[C:98]2[N:97]=[C:96]([Cl:99])[N:95]=[C:79]([NH:80][C@H:81]([CH3:94])[CH2:82][S:83][C:84]3[S:85][C:86]4[CH:92]=[CH:91][C:90]([Cl:93])=[CH:89][C:87]=4[N:88]=3)[C:78]=2[N:77]=[CH:76]1)(=O)C.C[O-].[Na+]>CO>[Cl:93][C:90]1[CH:91]=[CH:92][C:86]2[S:85][C:84]([S:83][CH2:82][C@H:81]([NH:80][C:79]3[C:78]4[N:77]=[CH:76][N:75]([C:98]=4[N:97]=[C:96]([Cl:99])[N:95]=3)[C@@H:62]3[O:63][C@H:64]([CH2:70][OH:71])[C@@H:65]([OH:66])[C@H:61]3[OH:60])[CH3:94])=[N:88][C:87]=2[CH:89]=1

Participants

7

Reactant 5

HCID 102530272,6-Dichloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)purineHCID 10942334Sodium MethoxideHCID 228583052',3',5'-tri-O-acetyl-2-chloro-N-[(R)-1-(5-chloro-2-benzothiazolyl)thio-2-propyl]adenosineHCID 677715022-[(R)-2-amino-1-propylthio]-5-chlorobenzothiazole hydrochlorideHCID 178527796HCID 178527796, compound

Product 1

HCID 22858280N-[(R)-1-(5-chloro-2-benzothiazolyl)thio-2-propyl]2-chloroadenosineYield 46%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

The title compound was prepared according to general method A as described above in Example 1 by reacting 2-[(R)-2-amino-1-propylthio]-5-chlorobenzothiazole hydrochloride [prepared by a Mitsunobu reaction as described in Example 1]with 2-[(R)-N-tert-butyloxycarbonyl]amino-1-propanol (1.75 g, 10 mmol) and 5-chloro-2-mercaptobenzothiazole (2.02 g, 10 mmol) followed by acidic hydrolysis] (0.5 g, 1.5 mmol) with 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (0.54 g, 1.2 mmol), followed by deacylation of the purified 2',3',5'-tri-O-acetyl-2-chloro-N-[(R)-1-(5-chloro-2-benzothiazolyl)thio-2-propyl]adenosine using sodium methoxide in methanol to provide the title N-[(R)-1-(5-chloro-2-benzothiazolyl)thio-2-propyl]2-chloroadenosine (0.30 g, 46%) as a solid, mp 145 ° C. (following column chromatography), 1H NMR (DMSO-d6) δ 1.39 (3H, d, --CHCH3), 3.45-3.78 (4H, m, H-5'a and H-5'b and --CH2 --), 3.96 (1H, q, H-4'), 4.14 (1H, t, H-3'), 4.52 (1H, t, H-2'), 4.72 (1H, m,-CH), 5.84 (1H, d, H-1'), 7.41 (1H, dd, Ar-H), 7.94 (1H, s, Ar-H), 8.02 (1H, dd, Ar-H), 8.42 (1H, s, H-8), 8.52 (1H, d, N--H). HPLC retention time 23.58 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-74a158218aae44408d1f189e44a2bd14
Source dataset
uspto-grants-1996_01
Patent number
US05484774

Reaction notes

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