Reaktion #338180

Reaktionsgleichung

HOBT

(S)-N1-(3,5-Dimethyl-pyridin-2-ylmethyl)-N1-(1-pyridin-2-yl-ethyl)-butane-1,4-diamine

6-hydroxy-nicotinic acid

DIPEA

EDCI

→

free base

Ausbeute 29.7%

(S)-N-{4-[(3,5-Dimethyl-pyridin-2-ylmethyl)-(1-pyridin-2-yl-ethyl)-amino]-butyl}-6-hydroxy-nicotinamide

Ausbeute 29.7%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigePurification of the crude material by radial chromatography on silica gel (1 mm plate, 10:1:1 CH2Cl2-MeOH—NH4OH)

Vorschrift

Using General Procedure G: To a solution of (S)-N1-(3,5-Dimethyl-pyridin-2-ylmethyl)-N1-(1-pyridin-2-yl-ethyl)-butane-1,4-diamine (0.11 g, 0.35 mmol) in dry DMF (7 mL) was added 6-hydroxy-nicotinic acid (79 mg, 0.57 mmol) followed by EDCI (115 mg, 0.59 mmol), HOBT (86 mg, 0.63 mmol), and DIPEA (0.20 mL, 1.15 mmol). Purification of the crude material by radial chromatography on silica gel (1 mm plate, 10:1:1 CH2Cl2-MeOH—NH4OH) provided 45 mg (29%) of the free base of the title compound as a colorless oil. Using General Procedure D: Conversion to the HBr salt gave COMPOUND 147 (49 mg, 62%) as a white solid. 1H NMR (D2O) δ 1.19-1.57 (m, 4H), 1.58 (d, 3H, J=6.9 Hz), 2.35 (s, 3H), 2.39 (s, 3H), 2.51-2.71 (m, 2H), 3.20 (t, 2H, J=6.3 Hz), 4.22 (s, 2H), 4.55 (q, 1H, J=6.9 Hz), 6.64 (d, 1H, J=9.6 Hz), 7.82 (dd, 1H, J=2.7, 9.6 Hz), 7.94-7.99 (m, 2H), 8.05-8.12 (m, 2H), 8.35 (s, 1H), 8.55 (dt, 1H, J=1.5, 8.1 Hz), 8.75 (dd, 1H, J=1.2, 5.7 Hz); 13C NMR (D2O) δ 14.53, 16.73, 17.45, 24.48, 26.53, 39.24, 51.26, 53.06, 60.39, 115.68, 119.28, 126.70, 135.93, 137.14, 137.29, 137.42, 140.95, 141.95, 148.01, 148.77, 149.56, 156.29, 165.39, 166.54; ES-MS m/z 434 (M+H). Anal. Calcd. For C25H31N5O2.3.5HBr.3.0H2O: C, 38.96; H, 5.30; N, 9.09; Br, 36.28. Found: C, 38.99; H, 5.29; N, 8.95; Br, 36.24.

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