5-Fluorouridine → HCID 67657349, compound

HRID 1957307Notes

Reaction equation

HRID 1957307 reaction equation
[F:1][C:2]1[C:3](=[O:18])[NH:4][C:5](=[O:17])[N:6]([CH:16]=1)[C@@H:7]1[O:15][C@H:12]([CH2:13][OH:14])[C@@H:10]([OH:11])[C@H:8]1[OH:9].[C:19]([NH:29][CH2:30][C:31](O)=[O:32])([O:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)=[O:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C>O1CCCC1.CN(C=O)C>[CH2:22]([O:21][C:19]([NH:29][CH2:30][C:31]([C@@:7]1([N:6]2[CH:16]=[C:2]([F:1])[C:3](=[O:18])[NH:4][C:5]2=[O:17])[O:15][C@H:12]([CH2:13][OH:14])[C@@H:10]([OH:11])[C@H:8]1[OH:9])=[O:32])=[O:20])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

7

Reactant 4

HCID 94275-FluorouridineHCID 11776TriphenylphosphineHCID 14349BenzyloxycarbonylglycineHCID 5363146Diisopropyl azodicarboxylate

Product 1

HCID 67657349HCID 67657349, compoundYield 27%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

5-Fluorouridine (0.300 g, 1.144 mmol, Sigma) was suspended in 4.0 mL of anhydrous tetrahydrofuran under nitrogen. Dry DMF (0.25 mL) was added. Slowly, the solid dissolved. Cbz glycine (0.239 g, 1.142 mmol, Aldrich), triphenylphosphine (0.300 g, 1.144 mmol), and DIAD (0.220 g, 1.088 mmol) were added. The yellow solution was stirred for 48 h. The solution was concentrated under reduced pressure and chromatographed eluting successively with 1:20 MeOH:CHCl3, 1:10 MeOH:CHCl3, then 1:5 MeOH:CHCl3 to provide 0.137 g (27%) of the title compound as a colorless oil. (The same reaction without the DMF as a cosolvent resulted in an isolated yield of only 13%): IR (TF) 3300 (br), 1710, 1670 cm-1 ; 1H NMR (300 MHz, methanol-d4) δ3.95 (s, 2H, NHCH2 CO), 4.05-4.20 (m, 3H, ribose H-2',3', 4'), 4.35-4.50 (m, 2H, ribose H-5'), 5.09 (s, 2H, benzylic H), 5.81 (m, 1 H, ribose H-1'), 7.25-7.40 (m, 5H, aromatic H), 7.83 (m, 1 H, vinylic H); 13C NMR (75 MHz, methanol-d4) δ43.41, 64.90, 67.82, 70.65, 74.99, 82.85, 91.43, 125.95 (d, J=34.7 Hz, C 4), 128.77, 128.97, 129.40, 137.86, 141.74 (d, J=234.3 Hz, C5), 150.74, 158.96, 159.24 (d, J=26.2, C4), 171.55; TLC (methanol-chloroform, 1:5) Rf =0.35; exact MS (El) calcd for C19H20N3O9F: m/z 453.1184. Found: m/z 453.1174.

Workup

  1. dissolutionSlowly, the solid dissolved
  2. concentrationThe solution was concentrated under reduced pressure
  3. customchromatographed
  4. washeluting successively with 1:20 MeOH

Sources & evidence

ORD record
ord-a496bdd77d7c4d72a467689ba726cbb1
Source dataset
uspto-grants-1998_07
Patent number
US05783689

Reaction notes

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