4-Toluenesulfonyl chloride → N3-Methyl-1-{8-[(E)-2-(4-isopropyl-1,3-thiazol-2-yl)-1-ethenyl]-4-oxo-4H-pyrido-[1,2-a]pyrimidin-2-yl)-3-piperidinecarboxamide

HRID 1828501Notes

Reaction equation

HRID 1828501 reaction equation
O[C:2]1[N:3]=[C:4]2[CH:12]=[C:11](/[CH:13]=[CH:14]/[C:15]3[S:16][CH:17]=[C:18]([CH:20]([CH3:22])[CH3:21])[N:19]=3)[CH:10]=[CH:9][N:5]2[C:6](=[O:8])[CH:7]=1.C1(C)C=CC(S(Cl)(=O)=O)=CC=1.C(N(CC)CC)C.Cl.[CH3:42][NH:43][C:44]([CH:46]1[CH2:51][CH2:50][CH2:49][NH:48][CH2:47]1)=[O:45]>O1CCCC1.CN(C)C1C=CN=CC=1.CN(C)C=O>[CH3:42][NH:43][C:44]([CH:46]1[CH2:51][CH2:50][CH2:49][N:48]([C:2]2[N:3]=[C:4]3[CH:12]=[C:11](/[CH:13]=[CH:14]/[C:15]4[S:16][CH:17]=[C:18]([CH:20]([CH3:22])[CH3:21])[N:19]=4)[CH:10]=[CH:9][N:5]3[C:6](=[O:8])[CH:7]=2)[CH2:47]1)=[O:45]

Participants

8

Reactant 4

HCID 73974-Toluenesulfonyl chlorideHCID 8471TriethylamineHCID 22063726N-methylpiperidine-3-carboxamide hydrochlorideHCID 1363468402-Hydroxy-8-[(E)-2-(4-isopropyl-1,3-thiazol-2-yl)-1-ethenyl]-4H-pyrido[1,2-a]pyrimidin-4-one

Product 1

HCID 86588134N3-Methyl-1-{8-[(E)-2-(4-isopropyl-1,3-thiazol-2-yl)-1-ethenyl]-4-oxo-4H-pyrido-[1,2-a]pyrimidin-2-yl)-3-piperidinecarboxamideYield 79.4%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

2-Hydroxy-8-[(E)-2-(4-isopropyl-1,3-thiazol-2-yl)-1-ethenyl]-4H-pyrido[1,2-a]-pyrimidin-4-one (157 mg, 0.501 mmol) was dissolved in anhydrous tetrahydrofuran (2.5 ml) and anhydrous dimethylformamide (2.5 ml), added with 4-dimethylamino-pyridine (80.0 mg, 0.651 mmol) and p-toluenesulfonyl chloride (105 mg, 0.551 mmol), and stirred at 0° C. for 1.5 hours. Subsequently, the reaction mixture was added with triethylamine (698 μl, 5.01 mmol) and N3-methyl-3-piperidinecarboxamide hydrochloride (448 mg, 2.50 mmol), and then the mixture was stirred at 60° C. for 5.5 hours. The reaction mixture was concentrated, added with saturated aqueous ammonium chloride, and then extracted with chloroform. The organic layer was dried over sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (chloroform:methanol=100:2→100:3, v/v) to obtain the title compound (174 mg, 79%).

Workup

  1. stirringthe mixture was stirred at 60° C. for 5.5 hours
  2. concentrationThe reaction mixture was concentrated
  3. additionadded with saturated aqueous ammonium chloride
  4. extractionextracted with chloroform
  5. dry with materialThe organic layer was dried over sodium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (chloroform

Sources & evidence

ORD record
ord-84c623e7f35a4636828d3493543d7b11
Source dataset
uspto-grants-2006_06
Patent number
US07056917B2

Reaction notes

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