4-Toluenesulfonyl chloride → N3,N3-Dimethyl-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 1828499Notes

Reaction equation

HRID 1828499 reaction equation
OC1N=C2C=C(/C=C/C3SC=C(C(C)C)N=3)C=CN2C(=O)C=1.[CH3:23][N:24]([CH3:59])[C:25]([CH:27]1[CH2:32][CH2:31][CH2:30][N:29]([C:33]2[N:34]=[C:35]3[CH:48]=[C:47](/[CH:49]=[CH:50]/[C:51]4[S:52][CH:53]=[C:54]([CH:56]([CH3:58])[CH3:57])[N:55]=4)[CH:46]=[CH:45][N:36]3[C:37](=[O:44])[C:38]=2/C=C/C(O)=O)[CH2:28]1)=[O:26].C1(C)C=CC(S(Cl)(=O)=O)=CC=1.C(N(CC)CC)C.FC(F)(F)C(O)=O.CN(C)C(C1CCCNC1)=O>O1CCCC1.CN(C)C1C=CN=CC=1.CN(C)C=O>[CH3:59][N:24]([CH3:23])[C:25]([CH:27]1[CH2:32][CH2:31][CH2:30][N:29]([C:33]2[N:34]=[C:35]3[CH:48]=[C:47](/[CH:49]=[CH:50]/[C:51]4[S:52][CH:53]=[C:54]([CH:56]([CH3:57])[CH3:58])[N:55]=4)[CH:46]=[CH:45][N:36]3[C:37](=[O:44])[CH:38]=2)[CH2:28]1)=[O:26]

Participants

9

Reactant 5

HCID 73974-Toluenesulfonyl chlorideHCID 8471Triethylamine2×HCID 229293733-[(Dimethylamino)carbonyl]piperidine trifluoroacetic acid salt2×HCID 86588132(E)-3-(2-(3-[(Dimethylamino)carbonyl]piperidino}-8-[(E)-2-(4-isopropyl-1,3-thiazol-2-yl)-1-ethenyl]-4-oxo-4H-pyrido[1,2-a]pyrimidin-3-yl)-2-propenoic acidHCID 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 86588130N3,N3-Dimethyl-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 71%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

The 2-hydroxy-8-[(E)-2-(4-isopropyl-1,3-thiazol-2-yl)-1-ethenyl]-4H-pyrido-[1,2-a]pyrimidin-4-one (164 mg, 0.523 mmol) obtained in Example 101, (E) was dissolved in anhydrous tetrahydrofuran (2.5 ml) and anhydrous dimethylformamide (2.5 ml), added with 4-dimethylaminopyridine (83.0 mg, 0.680 mmol) and p-toluenesulfonyl chloride (110 mg, 0.576 mmol), and then the mixture was stirred at 0° C. for 3 hours. Subsequently, the reaction solution was added with triethylamine (729 μl, 5.23 mmol) and N3,N3-dimethyl-3-piperidinecarboxamide trifluoroacetic acid salt (707 mg, 2.62 mmol) and stirred at 0° C. for 1 hour, at room temperature for 30 minutes and at 60° C. for 19 hours. Then, the reaction solution was added with triethylamine (40.0 μl , 0.287 mmol) and N3,N3-dimethyl-3-piperidinecarboxamide trifluoroacetic acid salt (400 mg, 1.48 mmol) and stirred at 60° C. for 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=100:1→100:3, v/v) to obtain the title compound (168 mg, 71%).

Workup

  1. stirringstirred at 0° C. for 1 hour, at room temperature for 30 minutes and at 60° C. for 19 hours
  2. stirringstirred at 60° C. for 5 hours
  3. concentrationThe reaction mixture was concentrated
  4. additionadded with saturated aqueous ammonium chloride
  5. extractionextracted with chloroform
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (chloroform

Sources & evidence

ORD record
ord-74d0c6062b4e4e2fbc20785a487796d7
Source dataset
uspto-grants-2006_06
Patent number
US07056917B2

Reaction notes

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