Triethylamine → HCID 66710459, Verbindung

HRID 1777501Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1777501
[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([OH:10])=O)=[N:6][CH:7]=1.Cl.Cl.[C:13]([C:15]1[CH:28]=[CH:27][C:18]([CH2:19][N:20]2[CH2:25][CH2:24][CH:23]([NH2:26])[CH2:22][CH2:21]2)=[CH:17][CH:16]=1)#[N:14].C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C)C=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]([NH:26][CH:23]2[CH2:24][CH2:25][N:20]([CH2:19][C:18]3[CH:27]=[CH:28][C:15]([C:13]#[N:14])=[CH:16][CH:17]=3)[CH2:21][CH2:22]2)=[O:10])=[N:6][CH:7]=1

Komponenten

6

Edukt 4

HCID 8471TriethylamineHCID 6085445-Bromopyridine-2-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 44120478HCID 44120478, Verbindung

Produkt 1

HCID 66710459HCID 66710459, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a solution of 5-bromopicolinic acid (0.50 g, 2.48 mmol, 1.0 eq) and 1-(4-cyanobenzyl)-4-aminopiperidine dihydrochloride (0.71 g, 2.48 mmol, 1.0 eq) in dimethylformamide (10 mL) was added triethylamine (1.21 mL, 8.66 mmol, 3.5 eq) and HATU (1.13 g, 2.97 mmol, 1.2 eq). The reaction mixture was stirred at room temperature 14 hours before partitioning between EtOAc (120 mL) and water (100 mL). The organics were washed with brine (100 mL), water (100 mL) and brine (100 mL), dried (Na2SO4) and concentrated under reduced pressure. MPLC (0%, 5%, 10% MeOH—CH2Cl2, 0→5→25→35 min) yielded 5-bromo-N-(1-(4-cyanobenzyl)piperidin-4-yl)picolinamide as a waxy brown solid: 1H nmr (CDCl3) 8.60 (1H, d, J 2.0 Hz, pyH-6), 8.07 (1H, d, J 8.5 Hz, pyH-3), 7.97 (1H, dd, J 8.5, 2.0 Hz, pyH-4), 7.84 (1H, d, J 7.5 Hz, NH), 7.63 (2H, d, J 8.5 Hz, 2H of C6H4CN), 7.50 (2H, d, J 8.0 Hz, 2H of C6H4CN), 4.00 (1H, m, pipH-4), 3.63 (2H, s, CH2C6H4CN), 2.88 (2H, m, 2H of pip), 2.30 (2H, m, 2H of pip), 2.04 (2H, m, 2H of pip), 1.70 (2H, m, 2H of pip); m/z 399, 401 [M+H]+. To a mixture of the 5-bromo-N-(1-(4-cyanobenzyl)piperidin-4-yl)picolinamide (0.040 g, 0.100 mmol, 1.0 eq) 4-(4-piperidinyloxy)benzonitrile (0.024 g, 0.120 mmol, 1.2 eq), sodium t-butoxide (0.019 g, 0.201 mmol, 2.0 eq) and S-Phos (0.004 g, 0.010 mmol, 0.1 eq) was added toluene (1.0 mL). The resulting mixture was degassed by bubbling argon through the mixture.

Aufarbeitung

  1. custombefore partitioning between EtOAc (120 mL) and water (100 mL)
  2. washThe organics were washed with brine (100 mL), water (100 mL) and brine (100 mL)
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-4cbcb5ba93b94ceaa67c7f9d64e12f3e
Quelldatensatz
uspto-grants-2016_02
Patentnummer
US09266856B2

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