Butylamine → Clevudine

HRID 985129Notes

Reaction equation

HRID 985129 reaction equation
C([O:9][C@H:10]1[C@H:14]([CH2:15][O:16]C(=O)C2C=CC=CC=2)[O:13][C@H:12]([N:25]2[CH:33]=[C:31]([CH3:32])[C:29](=[O:30])[NH:28][C:26]2=[O:27])[C@@H:11]1[F:34])(=O)C1C=CC=CC=1.C(N)CCC>CO>[F:34][C@@H:11]1[C@@H:10]([OH:9])[C@H:14]([CH2:15][OH:16])[O:13][C@@H:12]1[N:25]1[CH:33]=[C:31]([CH3:32])[C:29](=[O:30])[NH:28][C:26]1=[O:27]

Participants

4

Reactant 2

HCID 8007ButylamineHCID 106003591-(3,5-Di-O-benzoyl-2-deoxy-2-fluoro-β-L-arabinofuranosyl)-5-methyl-2,4(1H,3H)-pyrimidinedione

Product 1

HCID 73115Clevudine

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 23 (47 mg, 0.1 mmol) and n-butylamine (0.74 g, 1.0 mL, 10 mmol) in methanol (2 mL) was heated at reflux for 3 hours. The solution was evaporated to dryness and triturated with ethyl ether to afford a solid that was filtered, washed with ether and dried to afford 24 (20 mg, 0.077 mmol, 77% as a white solid: mp 188° C. (lit. value: mp 185-187° C., 184-185° C., 187-188° C. for the D-isomer); [α]D20=−93 (c 0.25 MeOH); (lit. value: [α]D20=−111 (c 0.23 MeOH), [α]D20=−122 (c0.023 MeOH)); 1H-NMR (DMSO-d6) δ 11.0 (1H, bs, N—H, 7.58 (1H, s, C—H thymine), 6.09 (1H, dd, J=4.2 and J=15.6, H-1), 5.85 (1H, bs, OH), 5.10 (1H, bs, OH), 5.02 (1H, dt, J−4.0, J−3.8 and J−52.8, H-2), 4.22 (1H, dt, J−3.8, J−4.0 and J=20.3, H-3), 3.76 (1H, q, J=4.0 and J−9.5, H-4), 3.69-3.57 (2H, m, H-5 and H-5′), 1.77 (3H, s, Thymine CH3).

Workup

  1. temperatureat reflux for 3 hours
  2. customThe solution was evaporated to dryness
  3. customtriturated with ethyl ether
  4. customto afford a solid
  5. filtrationthat was filtered
  6. washwashed with ether
  7. customdried

Sources & evidence

ORD record
ord-c5ad1f3839f64971a3b992672a2fc896
Source dataset
uspto-grants-2005_03
Patent number
US06870048B2

Reaction notes

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