Lithium iodide → 2-(1,1-Dioxothiazinan-2-yl)-N-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamide

HRID 720280Notes

Reaction equation

HRID 720280 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]([N:20]3[CH2:25][CH2:24][CH2:23][CH2:22][S:21]3(=[O:27])=[O:26])[N:13]([CH3:19])[C:14](=[O:18])[C:15]=2[O:16]C)=[O:9])=[CH:4][CH:3]=1.[I-].[Li+]>N1C(C)=CC(C)=CC=1C>[F:1][C:2]1[CH:29]=[CH:28][C:5]([CH2:6][NH:7][C:8]([C:10]2[N:11]=[C:12]([N:20]3[CH2:25][CH2:24][CH2:23][CH2:22][S:21]3(=[O:27])=[O:26])[N:13]([CH3:19])[C:14](=[O:18])[C:15]=2[OH:16])=[O:9])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 66321Lithium iodideHCID 58739064HCID 58739064, compound

Product 1

HCID 546820402-(1,1-Dioxothiazinan-2-yl)-N-[(4-fluorophenyl)methyl]-5-hydroxy-1-methyl-6-oxopyrimidine-4-carboxamideYield 52.3%

Reagents, catalysts & solvents 1

HCID 79532,4,6-TrimethylpyridineSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 2-(1,1-dioxo-1λ6-[1,2]thiazinan-2-yl)-5-methoxy-1-methyl-6-oxo-1,6-dihydro-pyrimidine-4-carboxylic acid 4-fluoro-benzylamide (0.115 g, 0.27 mmol) in 2,4,6-collidine (3 ml) was treated with lithium iodide (0.060 g) and the resulting mixture was heated at 120° C. for 30 min. The collidine was then evaporated in vacuo, the residue was diluted with a small volume of water and the pH was adjusted to a value of 7 with 0.1 N hydrochloric acid. The aqueous phase was extracted three times with dichloromethane and the combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on reversed phase silica gel (Waters, C-18, 125 A, elution with water-acetonitrile 7:3 to 6:4) to give 0.058 g (52% yield) of the title amide as a white solid; mp 226–227° C. (dichloromethane-ethanol).

Workup

  1. customThe collidine was then evaporated in vacuo
  2. additionthe residue was diluted with a small volume of water
  3. extractionThe aqueous phase was extracted three times with dichloromethane
  4. washthe combined organic extracts were washed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chromatography on reversed phase silica gel (Waters, C-18, 125 A,
  8. washelution with water-acetonitrile 7:3 to 6:4)

Sources & evidence

ORD record
ord-eb23988a48954a929563fb78fd4aac3c
Source dataset
uspto-grants-2006_11
Patent number
US07135467B2

Reaction notes

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