Triethylamine → N-[4-(3-Furyl)-5-(tetrahydropyran-4-ylcarbonyl)thiazol-2-yl]-2-methylpyridine-4-carboxamide

HRID 1967849Notes

Reaction equation

HRID 1967849 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([C:9]2[S:13][C:12]([NH2:14])=[N:11][C:10]=2[C:15]2[CH:19]=[CH:18][O:17][CH:16]=2)=[O:8])[CH2:3][CH2:2]1.Cl.[CH3:21][C:22]1[CH:23]=[C:24]([CH:28]=[CH:29][N:30]=1)[C:25](O)=[O:26].CCN=C=NCCCN(C)C.Cl.O.ON1C2C=CC=CC=2N=N1.C(N(CC)CC)C.C(=O)([O-])O.[Na+]>CN(C=O)C>[O:17]1[CH:18]=[CH:19][C:15]([C:10]2[N:11]=[C:12]([NH:14][C:25]([C:24]3[CH:28]=[CH:29][N:30]=[C:22]([CH3:21])[CH:23]=3)=[O:26])[S:13][C:9]=2[C:7]([CH:4]2[CH2:5][CH2:6][O:1][CH2:2][CH2:3]2)=[O:8])=[CH:16]1

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27628242-methylpyridine-4-carboxylic Acid HydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 866124732-Amino-4-(3-furyl)thiazol-5-yl tetrahydropyran-4-yl ketone

Product 1

HCID 23144391N-[4-(3-Furyl)-5-(tetrahydropyran-4-ylcarbonyl)thiazol-2-yl]-2-methylpyridine-4-carboxamideYield 51.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Compound 610 (100 mg, 0.359 mmol) was dissolved in DMF (3 mL), and 2-methylisonicotinic acid hydrochloride (249 mg, 1.44 mmol), EDC hydrochloride (558 mg, 2.91 mmol), 1-hydroxybenzotriazole monohydrate (463 mg, 3.02 mmol) and triethylamine (0.400 mL, 2.87 mmol) were added thereto, followed by stirring overnight at 80° C. The reaction mixture was poured into aqueous sodium hydrogencarbonate solution, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The resulting residue was purified through silica gel column chromatography (hexane:ethyl acetate=3:1), followed by recrystallizing from a mixed solvent of ethanol and water to afford the entitled Compound 615 (73.1 mg, 51%) as a white solid.

Workup

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with a saturated aqueous solution of sodium chloride
  3. dry with materialdried over anhydrous magnesium sulfate
  4. distillationthe solvent was distilled away under reduced pressure
  5. customThe resulting residue was purified through silica gel column chromatography (hexane:ethyl acetate=3:1)
  6. customby recrystallizing from a mixed solvent of ethanol and water

Sources & evidence

ORD record
ord-5507416d85e4410eb1365afd218a044d
Source dataset
uspto-grants-2013_04
Patent number
US08420827B2

Reaction notes

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