Diketene → HCID 69733596, compound

HRID 2416413Notes

Reaction equation

HRID 2416413 reaction equation
[C:1]([O:4][C@H:5]([CH3:20])[CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:15](=[O:16])[CH:14]=[C:13]([NH2:17])[N:12]([CH3:18])[C:11]1=[O:19])(=[O:3])[CH3:2].[CH2:21]=[C:22]1O[C:24](=[O:25])[CH2:23]1>ClCCCl>[C:1]([O:4][C@H:5]([CH3:20])[CH2:6][CH2:7][CH2:8][CH2:9][N:10]1[C:15](=[O:16])[C:14]2[C:24](=[O:25])[CH:23]=[C:22]([CH3:21])[NH:17][C:13]=2[N:12]([CH3:18])[C:11]1=[O:19])(=[O:3])[CH3:2]

Participants

4

Reactant 2

HCID 12661Diketene2×HCID 54017983HCID 54017983, compound

Product 1

HCID 69733596HCID 69733596, compoundYield 49%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A mixture of (R)-3-(5-acetoxyhexyl)-6-amino-1-methyluracil (500 mg, 1.77 mmol), 1,2-dichloroethane (5 ml) and diketene (0.14 ml, 1.77 mmol) was heated at reflux for 18 hours. Another portion of diketene (0.2 ml) was added and the mixture was heated at reflux for an additional 18 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel eluting with ethyl acetate-hexane (1:1) to provide (R)-3-(5-acetoxyhexyl)-1,7-dimethylpyrido[2,3-d]pyrimidine-2,4,5(1H,3H,8H)-trione (300 mg, 49% yield) as an oil. 1H NMR (300 MHz, CDCl3) δ 1.20 (d, 3H), 1.25-1.71 (m, 6H), 2.00 (s, 3H), 2.46 (s, 3H), 3.62 (s, 3H), 4.00 (t, 2H), 4.86 (sextet, 1H), 6.49 (s, 1H), 12.15 (s, 1H). 13C NMR (75 MHz, CDCl3) δ 19.64, 20.96, 22.46, 25.02, 27.19, 29.15, 35.19, 40.67, 70.29, 94.48, 105.71, 150.09, 150.73, 164.92, 165.18, 167.82, 170.15.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 18 hours
  3. temperaturethe mixture was heated
  4. temperatureat reflux for an additional 18 hours
  5. concentrationthe mixture was concentrated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel eluting with ethyl acetate-hexane (1:1)

Sources & evidence

ORD record
ord-7461998d680f43719f9cbd92e3dae274
Source dataset
uspto-grants-2004_11
Patent number
US06825180B2

Reaction notes

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