1,1'-Carbonyldiimidazole → 2-amino-N-(2,6-dioxo-piperidin-3-yl)-6-methyl-benzamide

A mixture of 2-amino-6-methylbenzoic acid (45 g, 297 mmol) and CDI (45 g, 278 mmol) in acetonitrile (500 mL) was stirred at room temperature for 1.5 hours. To the suspension, was added 3-amino-piperidine-2,6-dione hydrogen chloride (45 g, 273 mmol) and sodium hydrogen carbonate (34 g, 409 mmol), and the mixture was heated at 50° C. for 21 hours. The suspension was cooled to room temperature for 1 hour. The suspension was filtered. The solid was stirred with water (150 mL) and ethyl acetate (150 mL) for 3 hours. The suspension was filtered and washed with water (2×50 mL) and ethyl acetate (2×50 mL). The solid was dried in a vacuum oven overnight to give 2-amino-N-(2,6-dioxo-piperidin-3-yl)-6-methyl-benzamide as a white solid (41.3 g, 58% yield): HPLC, Waters Symmetry C-18, 3.9×150 mm, 5 μm, 1 mL/min, 240 nm, 5/95 grad to 95/5 for 5 min CH3CN/0.1% H3PO4, 4.44 (91%); 1H NMR (DMSO-d6) δ 1.98-2.17 (m, 5H, CH2, CH3) 2.51-2.56 (m, 1H, CHH), 2.74-2.86 (m, 1H, CHH), 4.68-4.77 (m, 1H, NCH), 5.18 (s, 2H, NH2), 6.38 (d, J=7 Hz, 1H, Ar), 6.50 (d, J=7 Hz, 1H, Ar), 6.94 (t; J=7 Hz, 1H, Ar), 8.59 (d, J=8 Hz, 1H, NH), 10.90 (s, 1H, NH); 13C NMR (DMSO-d6) δ 19.14, 23.75, 30.99, 49.10, 112.37, 17.21, 122.28, 128.96, 134.61, 145.22, 168.36, 172.84, 173.00; LCMS: MH=262.

1. temperaturethe mixture was heated at 50° C. for 21 hours
2. temperatureThe suspension was cooled to room temperature for 1 hour
3. filtrationThe suspension was filtered
4. stirringThe solid was stirred with water (150 mL) and ethyl acetate (150 mL) for 3 hours
5. filtrationThe suspension was filtered
6. washwashed with water (2×50 mL) and ethyl acetate (2×50 mL)
7. customThe solid was dried in a vacuum oven overnight

ORD-Eintrag

ord-2e6b0eff1f424c6c93ffec4c59b00b3f

Quelldatensatz

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08921385B2