1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 5-{3-[2-(Hydroxymethyl)-1H-indol-5-yl]-1,2,4-oxadiazol-5-yl}-2-[(1-methylethyl)oxy]benzonitrile

Temperature

80 °C

EDCI (144 mg) and HOBT (104 mg) were added to a solution of 3-cyano-4-[(1-methylethyl)oxy]benzoic acid (can be prepared as described in WO2005/58848, 144 mg) in DMF (5 mL) at RT. The resulting solution was stirred for 15 min. N-hydroxy-2-(hydroxymethyl)-1H-indole-5-carboximidamide (D25) (144 mg) was added and the reaction mixture was stirred at RT for 1 hour. The reaction mixture was heated to 80° C. and stirred at that temperature for 4 hours. EtOAc (50 mL) was added and the organic solution was washed with water (50 mL), saturated aqueous sodium bicarbonate solution (50 mL) and water (50 mL). The organic fraction was dried over anhydrous magnesium sulfate. The dried solution was concentrated. The residue was crystallized from EtOAc/ether to afford 5-{3-[2-(hydroxymethyl)-1H-indol-5-yl]-1,2,4-oxadiazol-5-yl}-2-[(1-methylethyl)oxy]benzonitrile (D26) (70 mg) as a pale brown solid. δH (DMSO-d6, 400 MHz): 1.39 (6H, d), 4.65 (2H, d), 4.99 (1H, m), 5.36 (1H, t) 6.46 (1H, s), 7.50 (1H, d), 7.56 (1H, d), 7.79 (1H, dd), 8.28 (1H, s), 8.43 (1H, dd), 8.51 (1H, d), 11.43 (1H, s). MS (ES): C21H18N4O3 requires 374; found 375.0 (M+H+).

1. stirringthe reaction mixture was stirred at RT for 1 hour
2. stirringstirred at that temperature for 4 hours
3. washthe organic solution was washed with water (50 mL), saturated aqueous sodium bicarbonate solution (50 mL) and water (50 mL)
4. dry with materialThe organic fraction was dried over anhydrous magnesium sulfate
5. concentrationThe dried solution was concentrated
6. customThe residue was crystallized from EtOAc/ether

ORD record

ord-1cacb0dfc063469f8e9c6befb150ce34

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08217028B2