Diisopropylethylamine → t-butyl [(2Z)-4-chloro-2-buten-1-yl]carbamate

Temperature

60 °C

Following the General Procedure for N-alkylation: To a solution of (1H-N-tert-butoxycarbonyl-benzimidazol-2-ylmethyl)-(5,6,7,8-tetrahydroquinolin-8-yl)-amine (200 mg, 0.53 mmol) and ((Z)-4-chloro-but-2-enyl)-carbamic acid Cert-butyl ester (130 mg, 0.64 mmol) in CH3CN (3 mL) were added N,N-diisopropylethylamine (138 μL, 0.80 mmol) and KI (4.4 mg, 0.027 mmol) and the reaction stirred at 60° C. for 18 h. The crude material was taken up in neat TFA (1 mL) and stirred 3 h. Saturated aqueous sodium bicarbonate (5 mL) was cautiously added, and the resulting mixture was extracted with CH2Cl2 (3×10 mL) then the combined organic extracts were dried (MgSO4), filtered and concentrated in vacuo. Purification of the crude material by radial chromatography (1 mm plate, 50:1:1 CH2Cl2—MeOH—NH4OH) afforded the title compound (57 mg, 31%) as a white solid. 1H NMR (CDCl3) δ 1.68-1.72 (m, 1H), 1.84-2.05 (m, 2H), 2.15-2.22 (m, 1H), 2.71 (dt, 1H, J=17, 5 Hz), 2.84 (ddd, 1H, J=16, 10, 5 Hz), 3.15-3.26 (m, 3H), 3.38 (dd, 1H, J=14, 7 Hz), 3.97-4.12 (m, 3H), 5.46-5.54 (m, 2H), 7.13 (dd, 1H, J=8, 5 Hz), 7.16-7.21 (m, 2H), 7.40 (dd, 1H, J=7, 1 Hz), 7.57 (br s, 2H), 8.57 (dd, 1H, J=5, 1 Hz); 13C NMR (CDCl3) δ 21.0, 22.9, 28.9, 37.4, 46.4, 48.6, 60.5, 115.0, 121.8, 122.2, 130.7, 131.6, 134.6, 137.4, 146.6, 154.2, 156.8. ES-MS m/z 348 (M+H). Anal. Calcd. for C21H25N5.0.1CHCl3.0.8CH4O: C, 68.32; H, 7.41; N, 18.19. Found: C, 68.60; 14, 7.05; N, 17.82.

1. stirringstirred 3 h
2. extractionthe resulting mixture was extracted with CH2Cl2 (3×10 mL)
3. dry with materialthe combined organic extracts were dried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customPurification of the crude material by radial chromatography (1 mm plate, 50:1:1 CH2Cl2—MeOH—NH4OH)

ORD record

ord-593eee49250c4397ac730b207260d5c5

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778967B2