1-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]piperidin-4-amine → 2-tert-Butyl-4-({1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}amino)-5-phenylisothiazol-3(2H)-one 1,1-dioxide

HRID 2239680Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2239680
[C:1]([N:5]1[C:9](=[O:10])[C:8](Cl)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])([CH3:4])([CH3:3])[CH3:2].[Cl:20][C:21]1[C:22]([N:31]2[CH2:36][CH2:35][CH:34]([NH2:37])[CH2:33][CH2:32]2)=[N:23][CH:24]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:26]=1>CN(C=O)C.CCOC(C)=O>[C:1]([N:5]1[C:9](=[O:10])[C:8]([NH:37][CH:34]2[CH2:33][CH2:32][N:31]([C:22]3[C:21]([Cl:20])=[CH:26][C:25]([C:27]([F:30])([F:29])[F:28])=[CH:24][N:23]=3)[CH2:36][CH2:35]2)=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[S:6]1(=[O:19])=[O:18])([CH3:4])([CH3:3])[CH3:2]

Komponenten

5

Edukt 2

HCID 27961851-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]piperidin-4-amineHCID 672426272-tert-Butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide

Produkt 1

HCID 116567902-tert-Butyl-4-({1-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]piperidin-4-yl}amino)-5-phenylisothiazol-3(2H)-one 1,1-dioxideAusbeute 78,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

2-tert-Butyl-4-chloro-5-phenylisothiazol-3(2H)-one 1,1-dioxide (200 mg, 0.667 mmol) was dissolved in dry DMF (2 mL) under nitrogen atmosphere. 1-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]piperidin-4-amine (188 mg, 0.674 mmol) was added followed by TEA (68 mg, 0.667 mmol) and the reaction mixture was heated in a microwave reactor at 120° C. for 20 mins. The reaction mixture was diluted with EtOAc, washed with saturated aqueous NaHCO3-solution, dried over Na2SO4, filtered and evaporated. The crude product was purified on a Biotage Horizon HPFC system using Heptane and EtOAc as eluant affording the title compound (284 mg, 77.6%). 1H NMR (500 MHz, CDCl3): δ 1.46-1.54 (m, 2H), 1.73-1.79 (m, 1H), 2.51 (t, 2H), 3.12-3.19 (m, 1H), 3.79-3.82 (m, 2H), 5.28 (d, 1H), 7.44-7.46 (m, 3H), 7.53-7.55 (m, 2H), 7.72 (s, 1H), 8.33 (s, 1H); 13C NMR (125 MHz, CDCl3): δ 27.82, 32.36, 47.43, 50.27, 61.80, 107.32, 120.35 (q, J=33.4 Hz), 121.28, 123.48 (q, J=271.3 Hz), 125.36, 128.94, 130.17, 131.85, 134.16, 136.15, 143.10, 159.87, 160.06; Mass Spectrum: M+H+ 543.1.

Aufarbeitung

  1. washwashed with saturated aqueous NaHCO3-solution
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude product was purified on a Biotage Horizon HPFC system

Quellen und Nachweise

ORD-Eintrag
ord-c011c248c89643e6920a76f2d26581c5
Quelldatensatz
uspto-grants-2010_05
Patentnummer
US07723333B2

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