Cyanoaryl-aniline compounds for treatment of dermal disorders
A kind of compound and mixture technology, applied in the field of cyanoaromatic-aniline compounds for treating skin diseases
- Summary
- Abstract
- Description
- Claims
- Application Information
AI Technical Summary
Problems solved by technology
Method used
Image
Examples
Embodiment 1
[0335] Example 1: 4-cyano-2-((2-fluoro-4-iodophenyl)amino)benzoic acid
[0336]
[0337] will be at -78°C in N 2 A stirred solution of 4-cyano-2-fluorobenzoic acid (3.0 g, 18.1 mmol) in THF (30 mL) was treated (dropwise) with LDA (2.0 M in THF, 27.2 mL, 54.5 mmol). After 20 min, a solution of 2-fluoro-4-iodoaniline (12.9 g, 54.5 mmol) in dry THF (15 mL) was added dropwise and the reaction mixture was continued to stir and allowed to warm to room temperature. After 16 h, the reaction mixture was concentrated in vacuo, acidified with 1M HCl and washed with Et 2 O extracted twice. The combined organic phases were washed with brine, washed with Na 2 SO 4 Dry, filter and concentrate in vacuo. The crude residue was purified by trituration in boiling DCM to give the product as a yellow solid (1.57 g, 22.7%). m / z 381.1[M-H] - . 1 H NMR (400MHz, DMSO-d 6 )δppm 13.91 (s, 1H), 9.74 (s, 1H), 8.04 (d, J = 8.2Hz, 1H), 7.77 (dd, J = 10.3, 2.0Hz, 1H), 7.58 (dt, J = 8.5, 1.3Hz, 1H...
Embodiment 2
[0338] Example 2: 4-cyano-2-((2-fluoro-4-iodophenyl)amino)benzoic acid
[0339]
[0340] A microwave vial was charged with 4-cyano-2-((2-fluoro-4-iodophenyl)amino)benzoic acid (80% pure) (0.19 g, 0.4 mmol), 3-hydroxyazetidine Hydrochloride (0.07g, 0.6mmol), HATU (0.25g, 0.6mmol) and diisopropylethylamine (140μL, 0.8mmol) and N,N-dimethylformamide (6mL). The reaction mixture was stirred overnight at room temperature. The reaction was quenched with water and extracted with ethyl acetate. The organics were washed with water, brine and dried over sodium sulfate. The solvent was evaporated. The residue was purified by flash chromatography (12 g silica gel, 0-5% methanol in dichloromethane) and then by reverse phase HPLC (30-95% acetonitrile / water) to give the product as a light yellow solid (71 mg, 41%) . m / z 438.1[M+1] + . 1 H NMR(300MHz,DMSO-d6):δ8.97(s,1H),7.69-7.65(dd,J=1.2Hz and 0.9Hz,1H),7.55-7.47(m,2H),7.40(s,1H ),7.28-7.18(m,2H),5.80(s,1H),4.45(s,1H),4.35(t,J=7.6...
Embodiment 16
[0345] Example 16: N-(azetidin-3-ylmethoxy)-4-cyano-2-((2-fluoro-4-iodophenyl)amino)benzamide
[0346]
[0347] Step 1: 3-(((4-cyano-2-((2-fluoro-4-iodophenyl)amino)benzamido)oxy)methyl)azacycle Butyl-1-carboxylate tert-butyl ester
[0348] 4-cyano-2-((2-fluoro-4-iodophenyl)amino)benzoic acid (0.100 g, 0.3 mmol) in N,N-dimethylformamide (3 mL) was charged in a microwave vial ), tert-butyl 3-((aminooxy)methyl)azetidine-1-carboxylate (60% pure) (0.13g, 0.4mmol), HATU (0.15g, 0.4mmol) and diisopropyl Diethylethylamine (135 μL, 0.8 mmol. The reaction mixture was stirred overnight at room temperature. The reaction was quenched with water and extracted with ethyl acetate. The organics were washed with water, brine, and dried over sodium sulfate. The solvent was evaporated. The residue was subjected to flash chromatography (12 g silica gel, 0-70% ethyl acetate in hexane). Product fractions were collected and solvent removed to give a yellow oil (77 mg, 52%). m / z 565.2 [M-1] ...
PUM
| Property | Measurement | Unit |
|---|---|---|
| molecular weight | aaaaa | aaaaa |
Abstract
Description
Claims
Application Information
Login to View More