Pyridine → HCID 87236973, compound

HRID 241243Notes

Reaction equation

HRID 241243 reaction equation
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:25][C@H:24]([CH2:26][O:27][C:28](=[O:35])[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C@@H:14]([O:15][C:16](=[O:23])[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C@H:12]2[OH:13])=[C:4]([NH2:36])[N:3]=1.N1C=CC=CC=1.[O:43](S(C(F)(F)F)(=O)=O)[S:44]([C:47]([F:50])([F:49])[F:48])(=O)=[O:45]>C(Cl)Cl>[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[CH:7][N:8]2[C@@H:11]2[O:25][C@H:24]([CH2:26][O:27][C:28](=[O:35])[C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C@@H:14]([O:15][C:16](=[O:23])[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[C@H:12]2[O:13][S:44]([C:47]([F:50])([F:49])[F:48])(=[O:45])=[O:43])=[C:4]([NH2:36])[N:3]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 87236957HCID 87236957, compound

Product 1

HCID 87236973HCID 87236973, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
10 °C

Procedure

To a heterogeneous mixture of crystallized 2-chloro-9-(3′,5′-di-O-benzoyl-β-D-ribofuranosyl)-adenine (F) (65 g, purity: 94.7% by A % HPLC, 120.7 mmol) in DCM (650 mL) and pyridine (65 mL) at about 0 to 20° C. under an atmosphere of N2(g) was added Tf2O (85.1 g, 301.6 mmol) dropwise whilst maintaining the temperature within the range of 0 to 20° C. The mixture turned clear and the reaction was deemed complete when the HPLC purity of F was not more than 1%. The mixture was washed with saturated NaHCO3 (325 mL) and the organic phase was washed with 2 N H2SO4 (325 mL) at room temperature The organic phase was dried using 3 Å molecule sieves until the Karl Fischer titration value was <=1000 ppm. The organic phase was evaporated in vacuo at 40° C. until about 290 g of residue (including about 130 mL of DCM) remained. The residue was directly used in the next step. The typical purity of 2-chloro-9-(3′,5′-di-O-benzoyl-2′-O-trifluoromethylsulfonyl-β-D-ribofuranosyl)-adenine (G) was >=95% and the yield was >=95%. 1H NMR (300 MHz, CDCl3) δ 8.11 (dd, J=8.3, 1.2 Hz, 2H), 7.98 (dd, J=8.3, 1.2 Hz, 2H), 7.87 (s, 1H), 7.70-7.60 (m, 1H), 7.59-7.46 (m, 3H), 7.41 (t, J=7.7 Hz, 2H), 6.34-6.23 (m, 2H), 6.16 (dd, J=5.3, 3.2 Hz, 1H), 6.07 (bs, 2H), 4.86 (dd, J=12.2, 3.3 Hz, 1H), 4.81-4.74 (m, 1H), 4.65 (dd, J=12.2, 4.2 Hz, 1H).

Workup

  1. washThe mixture was washed with saturated NaHCO3 (325 mL)
  2. washthe organic phase was washed with 2 N H2SO4 (325 mL) at room temperature The organic phase
  3. customwas dried
  4. customThe organic phase was evaporated in vacuo at 40° C. until about 290 g of residue (including about 130 mL of DCM)

Sources & evidence

ORD record
ord-75f9232b1af04b24a1420753ee9fc0be
Source dataset
uspto-grants-2014_02
Patent number
US08648188B2

Reaction notes

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