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

Reaktionsgleichung

Reaktionsgleichung von HRID 245223
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]

Komponenten

8

Edukt 5

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydride2×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

Produkt 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-quinolinecarboxamideAusbeute 67 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

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+).

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-42aef703dafa4dfd82000e84bb42a441
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658636B2

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