Pyridine → 1-(3-O-acetyl-2,5-dideoxy-5-iodo-beta-D-threopentofuranosyl)thymine

HRID 732879Notes

Reaction equation

HRID 732879 reaction equation
[C:1]([O:4][C@H:5]1[C@@H:9]([CH2:10][I:11])[O:8][C@@H:7]([N:12]2[CH:20]=[C:18]([CH3:19])[C:16](=[O:17])[NH:15][C:13]2=[O:14])[CH2:6]1)(=[O:3])[CH3:2].C[C:22](OC(C)=O)=[O:23].N1C=CC=C[CH:29]=1>>[CH3:19][C:18]1[C:16](=[O:17])[NH:15][C:13](=[O:14])[N:12]([C@@H:7]2[O:8][C@:9]([C:10]#[CH:29])([CH2:22][OH:23])[CH:5]=[CH:6]2)[CH:20]=1.[C:1]([O:4][C@H:5]1[C@@H:9]([CH2:10][I:11])[O:8][C@@H:7]([N:12]2[CH:20]=[C:18]([CH3:19])[C:16](=[O:17])[NH:15][C:13]2=[O:14])[CH2:6]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 121116121-(3-O-acetyl-2,5-dideoxy-5-iodo-beta-D-threopentofuranosyl)thymine

Product 2

HCID 30088972',3'-Didehydro-3'-deoxy-4'-ethynylthymidineHCID 121116121-(3-O-acetyl-2,5-dideoxy-5-iodo-beta-D-threopentofuranosyl)thymineYield 93%

Procedure

TKD-4-114 (2′,3′-didehydro-3′-deoxy-4′-ethynylthymidine, 4′-ethynyl-d4T) was synthesized by a series of reactions shown in Scheme B, starting from compound 6 which was prepared according to the published procedure: B. V. Joshi and C. B. Reese, Tetrahedron Lett., 32, 2371-2374 (1992).1-(3-O-Acetyl-2,5-dideoxy-5-iodo-β-D-threo-pentofuranosyl)-thymine (7) A mixture of 6 (5.3 g, 15.05 mmol) and Ac2O (4.3 mL, 45.15 mmol) in pyridine (30 mL) was stirred at room temperature for 13 h. The reaction mixture was partitioned between CHCl3/saturated aqueous NaHCO3 (250 mL×3/50 mL). Silica gel column chromatography (hexane/EtOAc=1/1-1/2) of the organic layer gave 7 (5.53 g, 93%) as a foam: 1H NMR(CDCl3)δ 1.96 (3H, s, Me), 2.11 (3H, s, Ac), 2.11-2.16 (1H, m, H-2′a), 2.82 (1H, ddd, Jgem=15.8 Hz, J1′,2′b=8.0 Hz ansd J2′b,3′=5.7 Hz, H-2′b), 3.32-3.39 (2H, m, H-5′), 4.28 (1H, dt, J3′,4′=3.3 Hz and J4′,5′=7.1 Hz, H-4′), 5.48 (1H, dd, J2′b,3′=5.7 Hz and J3′,4′=3.3 Hz H-3′), 6.30 (1H, dd, J1′,2′a=2.8 Hz and J1′,2′b=8.0 Hz, H-1′), 7.38 (1H, d, J6,Me=0.7 Hz, H-6), 8.59 (1H, br, NH); FAB-MS m/z 395(M++H).

Workup

  1. customwas prepared
  2. customThe reaction mixture was partitioned between CHCl3/saturated aqueous NaHCO3 (250 mL×3/50 mL)

Sources & evidence

ORD record
ord-75a5e396a2a64b4ebd416cb0a92c6eb2
Source dataset
uspto-grants-2009_09
Patent number
US07589078B2

Reaction notes

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