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 1828499ノート

反応式

HRID 1828499 の反応式
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]

参加物

9

反応物 5

HCID 73974-Toluenesulfonyl chlorideHCID 8471Triethylamine2 回HCID 229293733-[(Dimethylamino)carbonyl]piperidine trifluoroacetic acid salt2 回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

生成物 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-piperidinecarboxamide収率 71%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-74d0c6062b4e4e2fbc20785a487796d7
出典データセット
uspto-grants-2006_06
特許番号
US07056917B2

反応ノート

読み込み中…