5-Bromo-6-chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide → 5-Bromo-2-(4-(morpholine-4-carbonyl)phenylamino)-6-(piperidin-1-yl)nicotinamide

HRID 2044062Notes

Reaction equation

[Br:1][C:2]1[C:3](Cl)=[N:4][C:5]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[O:19])=[CH:14][CH:13]=2)=[C:6]([CH:10]=1)[C:7]([NH2:9])=[O:8]>N1CCCCC1.C(Cl)Cl>[Br:1][C:2]1[C:3]([N:4]2[CH2:5][CH2:6][CH2:10][CH2:2][CH2:3]2)=[N:4][C:5]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[O:19])=[CH:14][CH:13]=2)=[C:6]([CH:10]=1)[C:7]([NH2:9])=[O:8]

Participants

Conditions

Temperature: 70 °C

Procedure

A solution of 5-bromo-6-chloro-2-(4-(morpholine-4-carbonyl)phenylamino)nicotinamide (200 mg, 0.454 mmol) in piperidine (1 ml) was stirred at rt for 2 h and heated to 70° C. for 1 h. The mixture was diluted with CH2Cl2, washed with water three times, and concentrated. The residue was purified by chromatography (ISCO, hexane/ethyl acetate gradient, 40 g silica gel column) to give 210 mg of 5-bromo-2-(4-(morpholine-4-carbonyl)phenylamino)-6-(piperidin-1-yl)nicotinamide as a white solid. LCMS: (M+H)+=488.02, 489.96 (Br pattern). 1H NMR (400 MHz, CDCl3-MIX) δ ppm 11.11 (1H, s), 7.89 (1H, s), 7.76 (2H, d, J=8.79 Hz), 7.38 (2H, d, J=8.79 Hz), 3.72 (8H, br. s.), 3.46-3.52 (4H, m), 1.73 (6 H, m).

Workup

washwashed with water three times
concentrationconcentrated
customThe residue was purified by chromatography (ISCO, hexane/ethyl acetate gradient, 40 g silica gel column)

Sources & evidence

ORD record: ord-7747ba6d3af94c5fb5a7a921d79649f9
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08586751B2

Reaction notes

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