Hydrochloric Acid → 3-Amino-5-methoxy-[1,1'-biphenyl]-4-carboxamide

HRID 922391Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:5]=[C:6]([O:10][CH3:11])[C:7]=1[C:8]#[N:9].[OH-:18].[K+].Cl>CCO>[NH2:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:5]=[C:6]([O:10][CH3:11])[C:7]=1[C:8]([NH2:9])=[O:18]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 3-amino-5-methoxy-[1,1′-biphenyl]-4-carbonitrile (4, 0.64 g, 2.86 mmol) and KOH (1.12 g, 20 mmol) in EtOH (24 mL) in a sealed tube was heated at 100° C. for 18 h. Additional KOH (0.56 g, 10 mmol) was added and heating was continued for another 18 h. After this time, the mixture was cooled to room temperature, and the pH was adjusted to ˜2 by addition of concentrated HCl. After concentration, the residue was partitioned between ethyl acetate (100 mL) and water (50 mL). The extracts were washed with brine (50 mL), dried (Na2SO4), filtered, and concentrated. The residue was purified by silica gel chromatography eluting with methanol in dichloromethane (0-20%) to afford the title compound (0.28 g, 40%) as a yellow solid: 1H NMR (500 MHz, DMSO-d6) δ 7.62-7.60 (m, 2H), 7.58 (s, 1H), 7.47-7.44 (m, 2H), 7.39-7.36 (m, 1H), 7.28 (s, 1H), 6.61 (d, J=1.5 Hz, 1H), 6.56 (s, 2H), 6.43 (d, J=1.5 Hz, 1H), 3.87 (s, 3H); ESI MS m/z 243 [M+H]+.

Workup

temperatureheating
temperatureAfter this time, the mixture was cooled to room temperature
concentrationAfter concentration
customthe residue was partitioned between ethyl acetate (100 mL) and water (50 mL)
washThe extracts were washed with brine (50 mL)
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe residue was purified by silica gel chromatography
washeluting with methanol in dichloromethane (0-20%)

Sources & evidence

ORD record: ord-9c81eab7fcbd4bfa8f1dbf6683da426e
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09278940B2

Reaction notes

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