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

반응식

HRID 245223 반응식
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]

참가 물질

8

반응물 5

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydride2회HCID 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

생성물 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-quinolinecarboxamide수율 67%

시약·촉매·용매 2

HCID 6344Dichloromethane용매2회HCID 8857Ethyl Acetate용매2회

실험 절차

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+).

후처리

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

출처 및 근거

ORD 기록
ord-42aef703dafa4dfd82000e84bb42a441
출처 데이터셋
uspto-grants-2014_02
특허 번호
US08658636B2

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