1-(2,2,2-Trifluoroethyl)piperidin-4-amine → 6-(3-cyanophenyl)-N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]nicotinamide

HRID 602111

Reaktionsgleichung

Reaktionsgleichung von HRID 602111
[C:1]([C:3]1[CH:4]=[C:5]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][N:10]=2)[CH:6]=[CH:7][CH:8]=1)#[N:2].[F:18][C:19]([F:29])([F:28])[CH2:20][N:21]1[CH2:26][CH2:25][CH:24]([NH2:27])[CH2:23][CH2:22]1>CN(C)C=O>[C:1]([C:3]1[CH:4]=[C:5]([C:9]2[CH:17]=[CH:16][C:12]([C:13]([NH:27][CH:24]3[CH2:25][CH2:26][N:21]([CH2:20][C:19]([F:29])([F:18])[F:28])[CH2:22][CH2:23]3)=[O:15])=[CH:11][N:10]=2)[CH:6]=[CH:7][CH:8]=1)#[N:2]

Komponenten

4

Edukt 2

HCID 162287221-(2,2,2-Trifluoroethyl)piperidin-4-amine2×HCID 178779506-(3-Cyanophenyl)nicotinic acid

Produkt 1

HCID 597436286-(3-cyanophenyl)-N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]nicotinamideAusbeute 61,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel3×

Versuchsvorschrift

To a solution of 6-(3-cyanophenyl)nicotinic acid (50 mg, 0.222 mmol) in dimethylformamide (1 mL) was added 1,11-carbonylbis(1H-imidazole) (36.3 mg, 0.224 mmol) and the reaction mixture stirred at room temperature for 1 hour. A solution of 1-(2,2,2-trifluoroethyl)piperidin-4-amine (49 mg, 0.269 mmol) in dimethylformamide (0.5 mL) was then added and the reaction stirred overnight at room temperature. Further 1,11-carbonylbis(1H-imidazole) (18 mg, 0.132 mmol) was added and the reaction stirred for 30 minutes and then further 1-(2,2,2-trifluoroethyl)piperidin-4-amine (25 mg, 0.134 mmol) in dimethylformamide (0.5 mL) was added and the solution stirred for one hour. The dimethylformamide was evaporated off and the residue partitioned between ethyl acetate (10 mL) and water (3 mL). The organic layer was separated, dried over anhydrous MgSO4, filtered and evaporated to a white solid. This was triturated with t-butyl methyl ether and the white solid was filtered off and dried to give 6-(3-cyanophenyl)-N-[1-(2,2,2-trifluoroethyl)piperidin-4-yl]nicotinamide 53 mg 1H NMR (400 MHz, DMSO-d6) ppm 1.57-1.67 (m, 2H) 1.80-1.87 (m, 2H) 2.43-2.54 (m, 2H) 2.93-2.99 (m, 2H) 3.20 (q, J=10.1 Hz, 2H) 3.83 (m , 1H) 7.76 (t, J=8.2 Hz, 1H) 7.97 (m, 1H) 8.24 (m, 1H) 8.34 (dd, J=6.2, 2.4 Hz, 1H) 8.52 (m, 2H) 8.61*m, 1H) 9.12 (m, 1H) LCMS 389 (M+1) ELSD 1.27 minutes.

Aufarbeitung

  1. stirringthe reaction stirred overnight at room temperature
  2. stirringthe reaction stirred for 30 minutes
  3. stirringthe solution stirred for one hour
  4. customThe dimethylformamide was evaporated off
  5. customthe residue partitioned between ethyl acetate (10 mL) and water (3 mL)
  6. customThe organic layer was separated
  7. dry with materialdried over anhydrous MgSO4
  8. filtrationfiltered
  9. customevaporated to a white solid
  10. customThis was triturated with t-butyl methyl ether
  11. filtrationthe white solid was filtered off
  12. customdried

Quellen und Nachweise

ORD-Eintrag
ord-d8f0250862cc4edcb659abf0b30a2c07
Quelldatensatz
uspto-grants-2011_03
Patentnummer
US07902373B2

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