HCID 17756543, compound → HCID 67167609, compound

2-amino-N-methoxy-N-methyl-5-[2-(trimethylsilyl)ethynyl]benzamide (403 mg, 1.5 mmol, 1 eq.) and 3-(4-bromophenyl)-3-(trifluoromethyl)-1,2-bis(trimethylsilyl)diaziridine (synthesized by a 5-step process: Bender et al., 2007, 599 mg, 1.5 mmol, 1 eq.) were added together in a round-bottom flask and purged with nitrogen. THF was added, and the reaction was stirred at room temperature until all solids dissolved. The reaction was then cooled to −80° C. in a diethyl ether/dry ice bath, and 2.5 M n-butyllithium in hexanes (1.0 mL, 2.6 mmol, 1.8 eq.) was added, causing the reaction to turn a dark red color. The reaction was stirred at −80° C. for 2 hours and then quenched with saturated ammonium chloride solution (20 mL). The quenched reaction was extracted three times with ethyl acetate (50 mL each). The organic layer was then dried over sodium sulfate, and the solvent was evaporated. Purification on silica column (hexanes/ethyl acetate, 3:1→1:1) resulted in 342 mg (58%) of the title compound as a yellow solid. 1H NMR (500 MHz, CDCl3) δ 7.69 (dd, J=8.2, 37.0, 4H, Ar—H), 7.50 (d, J=1.8, 1H, Ar—H), 7.37 (dd, J=1.9, 8.6, 1H, Ar—H), 6.65 (d, J=8.6, 1H, Ar—H), 6.32 (s, 2H, NH2), 2.88 (d, J=8.6, 1H, CNH), 2.32 (d, J=8.8, 1H, CNH), 0.18 (s, 9H, Si(CH3)3). 13C NMR (126 MHz, CDCl3) δ 197.58 (CO), 151.25 (C—Ar), 141.43 (C—Ar), 138.23 (C—Ar), 138.06 (C—Ar), 134.66 (C—Ar), 129.57 (C—Ar), 128.37 (q, C—Ar, J=0.57), 123.55 (q, J=278.40, CF3), 117.35 (C—Ar), 117.19 (C—Ar), 110.28 (C—Ar), 104.90 (CSi(CH3)3), 92.18 (CCSi(CH3)3), 58.05 (q, J=36.3, C(NH)2), 0.25 (Si(CH3)3). Exact Mass, 403.13. 402.1046 [M−H]−, 404.1982 [M+H]+.

1. additionBender et al., 2007, 599 mg, 1.5 mmol, 1 eq.) were added together in a round-bottom flask
2. custompurged with nitrogen
3. additionTHF was added
4. dissolutiondissolved
5. temperatureThe reaction was then cooled to −80° C. in a diethyl ether/dry ice bath
6. customthe reaction
7. stirringThe reaction was stirred at −80° C. for 2 hours
8. customquenched with saturated ammonium chloride solution (20 mL)
9. customThe quenched reaction
10. extractionwas extracted three times with ethyl acetate (50 mL each)
11. dry with materialThe organic layer was then dried over sodium sulfate
12. customthe solvent was evaporated
13. customPurification on silica column (hexanes/ethyl acetate, 3:1→1:1)

ORD record

ord-f7b61e49aab94577bfa3f8d3b959eed6

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08980926B2