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

HRID 375160Notes

Reaction equation

HRID 375160 reaction equation
Cl.N[C@H](C)CSC1SC2C=C(OCC)C=CC=2N=1.C(OC1C=CC2N=C(S)SC=2C=1)C.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:64][C@@H:65]1[C@H:69]([O:70]C(=O)C)[C@@H:68]([CH2:74][O:75]C(=O)C)[O:67][C@H:66]1[N:79]1[C:104]2[N:103]=[C:102]([Cl:105])[N:101]=[C:83]([NH:84][C@H:85]([CH3:100])[CH2:86][S:87][C:88]3[S:89][C:90]4[CH:96]=[C:95]([O:97][CH2:98][CH3:99])[CH:94]=[CH:93][C:91]=4[N:92]=3)[C:82]=2[N:81]=[CH:80]1)(=O)C.C[O-].[Na+]>CO>[CH2:98]([O:97][C:95]1[CH:94]=[CH:93][C:91]2[N:92]=[C:88]([S:87][CH2:86][C@H:85]([NH:84][C:83]3[C:82]4[N:81]=[CH:80][N:79]([C:104]=4[N:103]=[C:102]([Cl:105])[N:101]=3)[C@@H:66]3[O:67][C@H:68]([CH2:74][OH:75])[C@@H:69]([OH:70])[C@H:65]3[OH:64])[CH3:100])[S:89][C:90]=2[CH:96]=1)[CH3:99]

Participants

7

Reactant 5

HCID 102530272,6-Dichloro-9-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)purineHCID 10942334Sodium MethoxideHCID 228583072',3',5'-tri-O-acetyl-2-chloro-N-[(R)-1-(6-ethoxy-2-benzothiazolyl)thio-2-propyl]adenosineHCID 677715722-[(R)-2-amino-1-propylthio]-6-ethoxybenzothiazole hydrochlorideHCID 178466040HCID 178466040, compound

Product 1

HCID 22858282N[(R)-1-(6-ethoxy-2-benzothiazolyl)thio-2-propyl]-2-chloroadenosineYield 17%

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]-6-ethoxybenzothiazole 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 6-ethoxy-2-mercaptobenzothiazole (4.23 g, 20 mmol) followed by acidic hydrolysis] (3.8 g, 11.1 mmol) with 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (1.1 g, 2.5 mmol), followed by deacylation of the purified 2',3',5'-tri-O-acetyl-2 -chloro-N-[(R)-1-(6-ethoxy-2-benzothiazolyl)thio-2-propyl]adenosine using sodium methoxide in methanol to provide the title N[(R)-1-(6-ethoxy-2-benzothiazolyl)thio-2-propyl]-2-chloroadenosine (0.22 g, 17%) as a foam (following column chromatography), 1H NMR (DMSO-d6) δ 1.32-1.40 (6H, m, --CH2CH3 and --CHCH3), 3.44-3.81 (4H, m, H-5'a and H-5'b and --CH2 --), 3.97 (1H, d, H-4'), 4.08 (2H, q, --CH2CH3), 4.14 (1H, d, H-3'), 4.53 (1H, q, H-2'), 4.68 (1H, m, --CH), 5.09 (1H, t, 5'-OH), 5.23, 5.51 (2H, 2d, 2'- and 3'-OH), 5.83 (1H, d, H-1'), 7.06, 7.57, 7.74 (3H, 3d, Ar-H), 8.42 (1H, s, H-8), 8.53 (1H, d, N--H). HPLC retention time 22.4 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-0d1cba4bf8f44b7a985d6a789633db57
Source dataset
uspto-grants-1996_01
Patent number
US05484774

Reaction notes

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