2-Mercaptoethanol → (2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-(2-hydroxyethylsulfanylmethyl)oxolane-3,4-diol

HRID 2254546Notes

Reaction equation

HRID 2254546 reaction equation
[H-].[Na+].[CH2:3]([OH:6])[CH2:4][SH:5].Cl[CH2:8][C@H:9]1[O:13][C@@H:12]([N:14]2[C:23]3[N:22]=[CH:21][N:20]=[C:18]([NH2:19])[C:17]=3[N:16]=[CH:15]2)[C@H:11]([OH:24])[C@@H:10]1[OH:25]>CN(C=O)C>[OH:6][CH2:3][CH2:4][S:5][CH2:8][C@H:9]1[O:13][C@@H:12]([N:14]2[C:23]3[N:22]=[CH:21][N:20]=[C:18]([NH2:19])[C:17]=3[N:16]=[CH:15]2)[C@H:11]([OH:24])[C@@H:10]1[OH:25]

Participants

5

Reactant 3

HCID 15672-MercaptoethanolHCID 24758Sodium hydrideHCID 53271185'-CHLORO-5'-DEOXYADENOSINE

Product 1

HCID 9862185(2R,3R,4S,5S)-2-(6-aminopurin-9-yl)-5-(2-hydroxyethylsulfanylmethyl)oxolane-3,4-diolYield 66%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a mixture of sodium hydride (1.5 g, 50% dispersion in oil, 31 mmol) in DMF (40 mL) was added 2-thioethanol (1.65 mL, 1.84 g, 24 mmol) dropwise, and the mixture was stirred under argon for 15 min at ambient temperature. 5'Chloro-5'-deoxyadenosine (1a) (4.3 g, 15 mmol) was added portion wise and stirring was continued overnight. The mixture was concentrated under reduced pressure and subjected to flash chromatography (MeOH/CHCl3, 3:7) to give the triol (1b) as a white solid (3.23 g, 66%) that was crystallized from EtOH to give colourless crystals of 1b with mp 198°-201° C.; UV (MeOH) max 259 nm (ε 15 900 ); 1H NMR (Me2SO-d6) δ 8.36 (s, 1, H8), 8.16 (s, 1, H2), 7.29 (br s, 2, NH2), 5.89 (d, J1'-2' =5.9 Hz, 1, H1'), 5.49 (d, JOH-2' =6.0 Hz, 1, OH2'), 5.31 (d, JOH-3' =5.0 Hz, 1, OH3'), 4.76 (t, J=5.5 Hz, 1, CH2OH), 4.75 ("q", J2'-3' =5.5 Hz, 1, H2'), 4.18 ("q", J3'-4' =4.8 Hz, 1, H3'), 4.02 (m, J4'-5'n =6.0 Hz, J4'-5'b =6.8 Hz, 1, H4'), 3.52 ("q", J=6.5 Hz, 2, CH2OH), 2.96 (m, J5'a-5'b =14.0 Hz, 1, H5'a), 2.85 (m, 1, H5'b), 2.60 (t, 2, SCH2); 13C NMR (Me2SO-d6) δ 155.97 (C6), 152.57 (C2), 149.36 (C4), 139.76 (C8), 119.06 (C5), 87.28 (C1'), 83.69 (C4'), 72.60, 72.44 (C3',3'), 60.76 (CH2OH), 34.55 (C5'), 34.19 (SCH2): MS m/z 327.0994 (M+ =327.1001). Anal. Calcd for C12H17N5O4S (327.4): C, 44.03; H, 5.23; N, 21.39; S, 9.79. Found: C, 43.91; H, 5.16; N, 21.52; S, 9.77.

Workup

  1. stirringstirring
  2. waitwas continued overnight
  3. concentrationThe mixture was concentrated under reduced pressure

Sources & evidence

ORD record
ord-434177479178494db73ab7d9aa0b18c9
Source dataset
uspto-grants-1993_08
Patent number
US05236902

Reaction notes

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