Sodium Methoxide → 2-chloro-N-[(S)-1-(2-benzothiazolyl)thio-2propyl]adenosine

HRID 375150Notes

Reaction equation

HRID 375150 reaction equation
Cl.N[C@@H](C)CSC1SC2C=CC=CC=2N=1.SC1SC2C=CC=CC=2N=1.C(O[C@@H]1[C@H](OC(=O)C2C=CC=CC=2)[C@@H](COC(=O)C2C=CC=CC=2)O[C@H]1N1C=NC2C1=NC(Cl)=NC=2Cl)(=O)C1C=CC=CC=1.C([O:78][C@@H:79]1[C@H:83]([O:84]C(=O)C2C=CC=CC=2)[C@@H:82]([CH2:93][O:94]C(=O)C2C=CC=CC=2)[O:81][C@H:80]1[N:103]1[C:125]2[N:124]=[C:123]([Cl:126])[N:122]=[C:107]([NH:108][C@@H:109]([CH3:121])[CH2:110][S:111][C:112]3[S:113][C:114]4[CH:120]=[CH:119][CH:118]=[CH:117][C:115]=4[N:116]=3)[C:106]=2[N:105]=[CH:104]1)(=O)C1C=CC=CC=1.C[O-].[Na+]>CO>[Cl:126][C:123]1[N:122]=[C:107]([NH:108][C@@H:109]([CH3:121])[CH2:110][S:111][C:112]2[S:113][C:114]3[CH:120]=[CH:119][CH:118]=[CH:117][C:115]=3[N:116]=2)[C:106]2[N:105]=[CH:104][N:103]([C:125]=2[N:124]=1)[C@@H:80]1[O:81][C@H:82]([CH2:93][OH:94])[C@@H:83]([OH:84])[C@H:79]1[OH:78]

Participants

7

Reactant 5

HCID 10942334Sodium MethoxideHCID 116930649-(2,3,5-tri-O-benzoyl-beta-D-ribofuranosyl)-2,6-dichloro-9H-purineHCID 228583182',3',5'-tri-O-benzoyl-2-chloro-N-[(S)-1-(2-benzothiazolyl)thio-2-propyl]adenosineHCID 677715852-[(S)-2-amino-1-propylthio]benzothiazole hydrochlorideHCID 178418395HCID 178418395, compound

Product 1

HCID 228582952-chloro-N-[(S)-1-(2-benzothiazolyl)thio-2propyl]adenosineYield 49%

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-[(S)-2-amino-1-propylthio]benzothiazole hydrochloride [prepared by a Mitsunobu reaction as laid out in Example 1 using 2-[(S)-N-tert-butyloxycarbonyl]amino-1-propanol (3.5 g, 20 mmol) and 2-mercaptobenzothiazole (3.35 g, 20 mmol) followed by acidic hydrolysis] (1.1 g, 4.2 mmol) with 9-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2,6-dichloro-9H-purine (2.8 g, 4.5 mmol), followed by debenzoylation of the purified 2',3',5'-tri-O-benzoyl-2-chloro-N-[(S)-1-(2-benzothiazolyl)thio-2-propyl]adenosine using sodium methoxide in methanol to provide the title 2-chloro-N-[(S)-1-(2-benzothiazolyl)thio-2propyl]adenosine (0.88 g, 49%) (following column chromatography), 1H NMR (DMSO-d6) δ 1.38 (3H, d, --CHCH3), 3.50-3.68 (4H, m, H-5'a, and H-5'b and --CH2 --), 3.95 (1H, d, H-4'), 4.12 (1H, d, H-3'), 4.51 (1H, q, H-2'), 5.07 (1H, t, 5'-OH), 5.22, 5.50 (2H, 2d, 2'- and 3'-OH), 5.83 (1H, d, H-1'), 7.34, 7.45 (2H, 2t, Ar-H), 7.85, 7.98 (2H, 2d, Ar-H), 8.40 (1H, s, H-8), 8.52 (1H, s, N--H). HPLC retention time 20.1 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-e6e7595629c54a43b8f0570a086af56c
Source dataset
uspto-grants-1996_01
Patent number
US05484774

Reaction notes

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