Sodium ethoxide → HCID 66748219, compound

HRID 2401815Notes

Reaction equation

HRID 2401815 reaction equation
Cl.[Cl:2][C:3]1[CH:23]=[CH:22][C:6]([CH2:7][C:8]2[N:9]=[C:10]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[S:11][C:12]=2[C:13](=[NH:15])[NH2:14])=[CH:5][CH:4]=1.[O-]CC.[Na+].C([O:30][C:31]([CH:33]=[CH:34][O-])=O)C.[Na+]>C(O)C>[Cl:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][C:8]2[N:9]=[C:10]([C:16]3[CH:21]=[CH:20][N:19]=[CH:18][CH:17]=3)[S:11][C:12]=2[C:13]2[NH:14][C:31](=[O:30])[CH:33]=[CH:34][N:15]=2)=[CH:22][CH:23]=1

Participants

5

Reactant 3

HCID 2723922Sodium ethoxideHCID 2367822458986-28-0HCID 66747935HCID 66747935, compound

Product 1

HCID 66748219HCID 66748219, compoundYield 12%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Procedure

To a solution of 4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazole-5-carboximidamide hydrochloride (188 mg, 0.515 mmol) in ethanol (8.0 mL) was added 21% sodium ethoxide in ethanol (0.192 mL, 0.515 mmol) and sodium 2-ethoxycarbonyl ethenolate (284 mg, 2.06 mmol) (prepared as in J. Med. Chem., (2001), 44(17), 2695-2700), and the reaction was heated to reflux overnight. The reaction was cooled and concentrated. The residue was slurried DCM (15 mL) and water (15 mL) for 20 minutes. The solids were filtered, dried and purified by silica gel chromatography (methanol/DCM=0/100→15/85) to give the product. HPLC gave 23 mg of the title compound as a yellow solid. (12% yield). LC/MS (FA) ES+ 381. 1H NMR (300 MHz, DMSO-d6) δ: 8.72-8.60 (m, 2H), 8.41 (d, 1H, J=5.7 Hz), 7.88-7.85 (m, 2H), 7.40-7.36 (m, 2H), 7.32-7.28 (m, 2H), 6.58 (d, 1H, J=5.7 Hz), 4.80 (s, 2H).

Workup

  1. temperaturethe reaction was heated
  2. temperatureto reflux overnight
  3. temperatureThe reaction was cooled
  4. concentrationconcentrated
  5. customfor 20 minutes
  6. filtrationThe solids were filtered
  7. customdried
  8. custompurified by silica gel chromatography (methanol/DCM=0/100→15/85)
  9. customto give the product

Sources & evidence

ORD record
ord-d17c6f7d8eec4fd6b023894c85480a5f
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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