2-Methyladenosine → N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]-2-methyladenosine

HRID 375152Notes

Reaction equation

HRID 375152 reaction equation
Cl[C:2]1[N:3]=[C:4]([NH:20][C@H:21]([CH3:33])[CH2:22][S:23][C:24]2[S:25][C:26]3[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=3[N:28]=2)[C:5]2[N:6]=[CH:7][N:8]([C:18]=2[N:19]=1)[C@@H:9]1[O:17][C@H:14]([CH2:15][OH:16])[C@@H:12]([OH:13])[C@H:10]1[OH:11].[C:34](O[C@@H]1[C@H](OC(=O)C)[C@@H](COC(=O)C)O[C@H]1N1C=NC2C1=NC(C)=NC=2Cl)(=O)C.CC1N=C(N)C2N=CN(C=2N=1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O.C[O-].[Na+]>CO>[S:25]1[C:26]2[CH:32]=[CH:31][CH:30]=[CH:29][C:27]=2[N:28]=[C:24]1[S:23][CH2:22][C@H:21]([NH:20][C:4]1[C:5]2[N:6]=[CH:7][N:8]([C:18]=2[N:19]=[C:2]([CH3:34])[N:3]=1)[C@@H:9]1[O:17][C@H:14]([CH2:15][OH:16])[C@@H:12]([OH:13])[C@H:10]1[OH:11])[CH3:33]

Participants

6

Reactant 4

HCID 4598902-MethyladenosineHCID 9936084Nnc-21-0136HCID 10942334Sodium MethoxideHCID 539815909-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)-6-chloro-2-methyl-9H-purine

Product 1

HCID 22858334N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]-2-methyladenosineYield 22.9%

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 described in Example 5) (0.89 g, 3.0 mmol) with 9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-6-chloro-2-methyl-9H-purine (1.07 g, 2.5 mmol) [prepared from 2-methylinosine (Journal of Organic Chemistry, 1967, 32, 3258-3260) by standard acylation and chlorination steps]. Deacylation of the purified 2',3',5'-tri-O-acetyl-N-[(R)-1-(2-benzothiazolyl)thio° 2-propyl]-2-methyladenosine using sodium methoxide in methanol to provide the desired N-[(R)-1-(2-benzothiazolyl)thio-2-propyl]-2-methyladenosine (0.28 g, 11%) (following column chromatography), 1H NMR (DMSO-d6) δ 1.40 (3H, d, --CHCH3), 2.30 (3H, S, --CH3), 3.50-3.77 (4H, m, H-5'a and H-5'b and --CH2 --), 3.98 (1H, d, H-4'), 4.13 (1H, d, H-3'), 4.63 (1H, q, H-2'), 4.86 (1H, br, --CHCH3), 5.19, 5.42 (2H, 2d, 2'- and 3'-OH), 5.70 (1H, t, 5'-OH), 5.85 (1H, d, H-1'), 7.36, 7.47 (2H, 2t, Ar-H), 7.80-7.96 (2H, m, Ar-H), 8.0 (1H, s, N--H), 8.26 (1H, s, H-8), 8.52 (1H, s, N--H). HPLC retention time 22.4 min [gradient elution, 20-80% acetonitrile/water (containing 0.1% TFA)]. C21H24N6O4S2.H2O requires C, 49.8; H, 4.8; N, 16.6. Found: C, 49.9; H, 5.1; N, 16.4%.

Workup

  1. customThe title compound was prepared

Sources & evidence

ORD record
ord-736ff1fc45bb4154a67b1be57a0b4009
Source dataset
uspto-grants-1996_01
Patent number
US05484774

Reaction notes

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