Acetic Acid → N-(3-Trifluoromethyl-4-benzyloxyphenyl)-6-[5-({[2-(methanesulphonyl)ethyl]amino}methyl)-4-furyl]-4-quinazolinamine

The mixture of 5-(4-(4-benzyloxy-3-trifluoromethylphenylamino)-quinazolin-6-yl)-furan-2-carbaldehyde (211 mg, 0.40 mmol), 2-methanesulphonyl-ethylamine (99 mg, 2.0 mmol), acetic acid (0.5 ml) in dichloromethane (15 ml) was stirred at room temperature for 1.5 hours then was heated to reflux for 1 hour. The mixture was cooled to 0° C. with ice bath. Sodium cyanoborohydride (50 mg, 0.8 mmol) was added at 0° C. The reaction mixture then was stirred at room temperature for 1 hour. Diluted with ethyl acetate (50 ml), then quenched with saturated sodium bicarbonate solution slowly. Extracted with ethyl acetate and the combined organic extracts were washed with brine, dried over MgSO4 and concentrated in vacuo. Purification of the resulting residue was accomplished using flash chromatography on silica gel with 2% methanol in ethyl acetate which afforded a yellow solid (0.10 g, 43% yield). H1 NMR (400 MHz, DMSO). δ10.0 (s, 1H), 8.7 (s, 1H), 8.5 (s, 1H), 8.1 (d, 1H), 8.1 (s, 2H), 7.8 (d, 1H), 7.4 (m, 5H), 7.3 (m, 1H), 7.0 (d, 1H), 6.5 (d, 1H), 5.3 (s, 2H), 3.8 (s, 2H), 3.2 (m, 2H), 3.0 (s, 3H), 2.9 (m, 2H). ESI-MS m/z 597 (M+H)+.

1. temperaturethen was heated
2. temperatureto reflux for 1 hour
3. temperatureThe mixture was cooled to 0° C. with ice bath
4. stirringThe reaction mixture then was stirred at room temperature for 1 hour
5. customquenched with saturated sodium bicarbonate solution slowly
6. extractionExtracted with ethyl acetate
7. washthe combined organic extracts were washed with brine
8. dry with materialdried over MgSO4
9. concentrationconcentrated in vacuo
10. customPurification of the resulting residue

ORDレコード

ord-b52b75527996487eaa213755a3015be1

出典データセット

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08513262B2