1-Hydroxybenzotriazole → 3-({[2-amino-5-(trifluoromethyl)phenyl]carbamoyl}methyl)-N-methoxy-N-methylcyclobutane-1-carboxamide

Temperatur

0 °C

TEA (1.49 ml, 10.70 mmol) was added to a suspension of 2-{3-[methoxy(methyl)carbamoyl]cyclobutyl}acetic acid, EDC.HCl 1.18 g, 6.20 mmol), HOBt.xH2O (0.77 g, 5.69 mmol) in DCM (20 ml) at 0° C. and stirred for 5 min before the addition of 4-(trifluoromethyl)benzene-1,2-diamine (1.04 g, 10.34 mmol). This was stirred for a further 20 min at 0° C. then allowed to warm to RT. The reaction was monitored by LC MS, after 2 hours the reaction mixture was washed with 1N HCl (50 ml) then sat. NaHCO3 (50 ml). This was dried over Na2SO4, filtered and evaporated to dryness. Purification by silica gel column chromatography, eluting with EtOAc gave the desired product (0.83 g, 44%) as a beige solid; MS (ESI+) for C16H20N3O3 m/z 360.00 [M+H]+; HPLC purirty 90% (ret. time, 1.64 min); 1H NMR (500 MHz, MeOD) δH ppm 2.02-2.16 (2H, m), 2.31-2.68 (4H, m), 2.69-2.88 (1H, m), 3.18 (3H, d, J=4.41 Hz), 3.36-3.59 (1H, m), 3.65-3.76 (3H, m), 6.81-6.97 (1H, m), 7.02-7.27 (1H, m), 7.28-7.48 (1H, m).

1. temperatureto warm to RT
2. waitThe reaction was monitored by LC MS, after 2 hours
3. washthe reaction mixture was washed with 1N HCl (50 ml)
4. dry with materialThis was dried over Na2SO4
5. filtrationfiltered
6. customevaporated to dryness
7. customPurification by silica gel column chromatography
8. washeluting with EtOAc

ORD-Eintrag

ord-23f2b553f53f47b8a13204f3d4d36477

Quelldatensatz

uspto-grants-2015_08

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09096634B2