Diisopropylethylamine → 6-[(1-methylethyl)sulfonyl]-3-[(3-methyl-4-oxo-1-piperidinyl)methyl]-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide

HRID 245223

反応式

HRID 245223 の反応式
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.C(N(CC)C(C)C)(C)C.[F:28][C:29]([F:39])([F:38])[C@H:30]([NH2:37])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.[CH3:40][CH:41]([S:43]([C:46]1[CH:47]=[C:48]2[C:53](=[CH:54][CH:55]=1)[N:52]=[C:51]([C:56]1[CH:61]=[CH:60][CH:59]=[C:58]([C:62]([F:65])([F:64])[F:63])[CH:57]=1)[C:50]([CH2:66][N:67]1[CH2:72][CH2:71][C:70](=[O:73])[CH:69]([CH3:74])[CH2:68]1)=[C:49]2[C:75](O)=[O:76])(=[O:45])=[O:44])[CH3:42].CCCP(=O)=O>C(OCC)(=O)C.ClCCl>[CH3:42][CH:41]([S:43]([C:46]1[CH:47]=[C:48]2[C:53](=[CH:54][CH:55]=1)[N:52]=[C:51]([C:56]1[CH:61]=[CH:60][CH:59]=[C:58]([C:62]([F:63])([F:65])[F:64])[CH:57]=1)[C:50]([CH2:66][N:67]1[CH2:72][CH2:71][C:70](=[O:73])[CH:69]([CH3:74])[CH2:68]1)=[C:49]2[C:75]([NH:37][C@H:30]([C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)[C:29]([F:38])([F:39])[F:28])=[O:76])(=[O:44])=[O:45])[CH3:40]

参加物

8

反応物 5

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydride2 回HCID 11789718(alphaR)-alpha-(Trifluoromethyl)benzenemethanamineHCID 16167369Propylphosphoric anhydrideHCID 674172316-[(1-Methylethyl)sulfonyl]-3-[(3-methyl-4-oxo-1-piperidinyl)methyl]-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

生成物 1

HCID 866756086-[(1-methylethyl)sulfonyl]-3-[(3-methyl-4-oxo-1-piperidinyl)methyl]-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide収率 67%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒2 回HCID 8857Ethyl Acetate溶媒2 回

実験手順

T3P (propylphosphonic anhydride) (0.698 mL of a 50% solution in ethyl acetate, 1.185 mmol), N,N-diisopropylethylamine (0.478 mL, 2.73 mmol), and [(1R)-2,2,2-trifluoro-1-phenylethyl]amine (0.251 g, 1.185 mmol) were added to a suspension of 6-[(1-methylethyl)sulfonyl]-3-[(3-methyl-4-oxo-1-piperidinyl)methyl]-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (0.5 g, 0.911 mmol) in dichloromethane (14.02 mL) at 0° C. After 90 min, additional T3P (propylphosphonic anhydride, 0.349 mL of a 50% solution in ethyl acetate, 0.593 mmol) was added. The mixture was stirred overnight at room temperature. The mixture was diluted with methylene chloride (30 mL), and the solution was washed with 10% Na2CO3, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was loaded onto florisil and purified using column chromatography (ISCO, 12 g silica, 5-40% ethyl acetate/hexanes) to afford 6-[(1-methylethyl)sulfonyl]-3-[(3-methyl-4-oxo-1-piperidinyl)methyl]-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.431 g, 67% yield). MS (m/z) 706.3 (M+H+).

後処理

  1. washthe solution was washed with 10% Na2CO3
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. custompurified

出典と根拠

ORDレコード
ord-42aef703dafa4dfd82000e84bb42a441
出典データセット
uspto-grants-2014_02
特許番号
US08658636B2

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