Pyridine → 3',5'-DI-O-Mesylthymidine

HRID 654262Notes

Reaction equation

HRID 654262 reaction equation
[C@@H:1]1([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[O:8][C@H:5]([CH2:6][OH:7])[C@@H:3]([OH:4])[CH2:2]1.N1C=CC=CC=1.[CH3:24][S:25](Cl)(=[O:27])=[O:26]>O>[CH3:24][S:25]([O:4][C@@H:3]1[C@@H:5]([CH2:6][O:7][S:25]([CH3:24])(=[O:27])=[O:26])[O:8][C@@H:1]([N:9]2[CH:17]=[C:15]([CH3:16])[C:13](=[O:14])[NH:12][C:10]2=[O:11])[CH2:2]1)(=[O:27])=[O:26]

Participants

5

Reactant 3

HCID 1049PyridineHCID 5789ThymidineHCID 31297Methanesulfonyl chloride2×

Product 1

HCID 105729323',5'-DI-O-MesylthymidineYield 81.2%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 3 liter, 3 necked round-bottomed flask was equipped with an overhead stirrer and paddle, a 500 mL dropping funnel and a Claisen adapter containing a drying tube and a thermometer. Thymidine (200 g, 0.82M) and pyridine (750 mL) were added to the flask. The mixture was stirred and warmed with a water bath (20 mins) to give a clear solution. The solution was then cooled in an ice bath to 0°-3° C. and the dropping funnel was charged with methanesulfonyl chloride (206.5 g, 1.08M). The methanesulfonyl chloride was then added dropwise over 40 minutes with no noticeable exotherm. The solution was stirred at 0° C. for 1 hr and then stored at 5° C. for 18 hr. The light brown mixture was then poured onto rapidly stirred water (3 L) containing ice (approx. 500 g). The desired product crystallised immediately. After stirring for 0.5 hr, the product was collected by filtration and washed several times with water (3×100 mL). The white solid was then dried under vacuum overnight (crude weight, 322 g, 98% yield). The product was recrystallised from hot acetone to give 267 g of a white solid (81% yield), mp 169°-171° C. (lit. 170°-171° C.). 1H NMR (360 MHz, d6 -DMSO) 11.40 (s, 1H, NH), 7.50 (s, 1H, H-6), 6.21 (t, 1H, H-1'), 5.29 (m, 1H, H-3'), 4.45 (m, 2H, H-5'), 4.35 (m, 1H, H-4'), 3.31 (s, 6 H, SO2CH3), 2.50 (m, 2H, H-2'), 1.78 (s, 3H, CH3) Analysis (C12H18N2O9S2) C, H, N.

Workup

  1. customA 3 liter, 3 necked round-bottomed flask was equipped with an overhead stirrer
  2. additiona Claisen adapter containing a drying tube
  3. temperaturewarmed with a water bath (20 mins)
  4. customto give a clear solution
  5. temperatureThe solution was then cooled in an ice bath to 0°-3° C.
  6. stirringThe solution was stirred at 0° C. for 1 hr
  7. customThe desired product crystallised immediately
  8. stirringAfter stirring for 0.5 hr
  9. filtrationthe product was collected by filtration
  10. washwashed several times with water (3×100 mL)
  11. customThe white solid was then dried under vacuum overnight (crude weight, 322 g, 98% yield)
  12. customThe product was recrystallised from hot acetone

Sources & evidence

ORD record
ord-bf272a775f2c4c22b586b0c584d00e2b
Source dataset
uspto-grants-1992_07
Patent number
US05130421

Reaction notes

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