[NH2:1][C:2]1([CH2:9][C:10]([O:12][CH3:13])=[O:11])[CH2:7][CH2:6][CH2:5][N:4]([CH3:8])[CH2:3]1.CC[N:16]([CH:20](C)C)[CH:17]([CH3:19])[CH3:18].ClC(Cl)([O:26]C(=O)OC(Cl)(Cl)Cl)Cl.[CH2:35](NC1C=CC=CC=1)[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42].[CH2:50]1[CH2:54]OC[CH2:51]1>>[CH3:8][N:4]1[CH2:5][CH2:6][CH2:7][C:2]([CH2:9][C:10]([O:12][CH3:13])=[O:11])([NH:1][C:20]([NH:16][C:17]2[CH:18]=[CH:54][C:50]([CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42])=[CH:51][CH:19]=2)=[O:26])[CH2:3]1A solution of methyl 2-(3-amino-1-methylpiperidin-3-yl)acetate (235 mg, 1.3 mmol) in and THF (10 mL), at 0° C., under N2, was treated with DIPEA (0.22 mL, 1.3 mmol) and triphosgene (133 mg, 0.45 mmol), in one portion. The reaction was stirred at 0° C. for a few min and then at rt for 110 min. The reaction was cooled to 0° C., treated with the N-octylaniline (0.29 mL, 1.3 mmol) followed by DIPEA (0.22 mL, 1.3 mmol). After 5 min the cooling bath was removed and the reaction was diluted with and THF (10 mL). Stirring was continued at rt overnight. The reaction was then concentrated under reduced pressure and purified by flash chromatography on silica gel using 0-12% MeOH/DCM as the eluent to isolate the title product as a white solid (0.296 g, 56%). 1H NMR (400 MHz, CD3OD) δ ppm 7.20 (d, J=8.59 Hz, 2 H), 7.05 (d, J=8.34 Hz, 2 H), 3.64 (s, 3 H), 2.89 (m, 2 H), 2.76 (br. s., 1 H), 2.54 (t, J=7.58 Hz, 2 H), 2.27 (s, 3 H), 1.97-2.23 (m, 3 H), 1.67-1.85 (m, 1 H), 1.50-1.66 (m, 3 H), 1.30 (d, J=7.33 Hz, 12 H), 0.89 (t, J=6.82 Hz, 3 H). MS ESI [M+H]+, calcd for [C24H39N3O3+H] 418.59 found m/z 418.3 (100).
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