Nnc-21-0136 → N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]-2-bromoadenosine

HRID 375151Notes

Reaction equation

HRID 375151 reaction equation
ClC1N=C(N[C@H](C)CSC2SC3C=CC=CC=3N=2)C2N=CN(C=2N=1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O.BrC1N=C2C(N=CN2[C@@H]2O[C@H](COC(=O)C)[C@@H](OC(=O)C)[C@H]2OC(=O)C)=C(Cl)N=1.C([O:66][C@@H:67]1[C@H:71]([O:72]C(=O)C)[C@@H:70]([CH2:76][O:77]C(=O)C)[O:69][C@H:68]1[N:81]1[C:103]2[N:102]=[C:101]([Br:104])[N:100]=[C:85]([NH:86][C@H:87]([CH3:99])[CH2:88][S:89][C:90]3[S:91][C:92]4[CH:98]=[CH:97][CH:96]=[CH:95][C:93]=4[N:94]=3)[C:84]=2[N:83]=[CH:82]1)(=O)C.C[O-].[Na+]>CO>[S:91]1[C:92]2[CH:98]=[CH:97][CH:96]=[CH:95][C:93]=2[N:94]=[C:90]1[S:89][CH2:88][C@H:87]([NH:86][C:85]1[C:84]2[N:83]=[CH:82][N:81]([C:103]=2[N:102]=[C:101]([Br:104])[N:100]=1)[C@@H:68]1[O:69][C@H:70]([CH2:76][OH:77])[C@@H:71]([OH:72])[C@H:67]1[OH:66])[CH3:99]

Participants

6

Reactant 4

HCID 9936084Nnc-21-0136HCID 10942334Sodium MethoxideHCID 15279882[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(2-bromo-6-chloropurin-9-yl)oxolan-2-yl]methyl acetateHCID 228582992',3',5'-tri-O-acetyl-2-bromo-N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]adenosine

Product 1

HCID 22858289N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]-2-bromoadenosineYield 14%

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]benzothiazole hydrochloride (prepared as indicated in Example 5) (1.07 g, 3.6 mmol) with 2-bromo-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-6-chloro-9H-purine (see WO 93/08206; Bioorganic and Medicinal Chemistry Letters, 1993, 3, 2661-2666) (1.48 g, 3.0 mmol) followed by deacylation of the purified 2',3',5'-tri-O-acetyl-2-bromo-N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]adenosine using sodium methoxide in methanol to provide the title N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]-2-bromoadenosine (0.20 g, 14%) as a foam (following column chromatography), 1H NMR (DMSO-d6) δ 1.38 (3H, d, --CHCH3), 3.50-3.77 (4H, m, H-5'a, and H-5'b and --CH2 --), 3.94 (1H, d, H-4'), 4.12 (1 H, d, H-3'), 4.51 (1H, q, H-2'), 4.70 1H, m, --CHCH3), 5.05 (1H, t, 5'-OH), 5.22, 5.49 (2H, 2d, 2'- and 3'-OH), 5.83 (1H, d, H-1'), 7.36, 7.46 (2H, 2t, Ar-H), 7.86, 7.99 (2H, 2d, Ar-H), 8.40 (1H, s, H-8). HPLC retention time 6.74 min [gradient elution, 20-80% acetonitrile/water (containing 0.1% TFA)].

Workup

  1. customThe title compound was prepared

Sources & evidence

ORD record
ord-65de66eb0d61454fb924739556e8c4d0
Source dataset
uspto-grants-1996_01
Patent number
US05484774

Reaction notes

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