Piperidine → HCID 57489612, compound

HRID 2044060Notes

Reaction equation

HRID 2044060 reaction equation
Cl[C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([NH2:8])=[O:7])=[C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[N:3]=1.[NH:20]1[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1>C(Cl)Cl>[F:11][C:10]1[C:2]([N:20]2[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]2)=[N:3][C:4]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)=[C:5]([CH:9]=1)[C:6]([NH2:8])=[O:7]

Participants

4

Reactant 2

HCID 8082PiperidineHCID 57489614HCID 57489614, compound

Product 1

HCID 57489612HCID 57489612, compoundYield 85.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

A solution of 6-chloro-5-fluoro-2-(4-fluorophenylamino)nicotinamide (50 mg, 0.176 mmol) and piperidine (1 mL, 10.12 mmol) was sealed in a small microwave vial and heated in a heating block at 100° C. for 2 hrs. The reaction mixture was diluted with CH2Cl2 and washed with bicarbonate and water. The reaction mixture was concentrated and the dark crude material was chromatographed (ISCO Companion 40 g silica gel column and eluted with (90:9:1 CH2Cl2:MeOH: NH4OH)t/CH2Cl2 gradient (20-100%)) to give 50 mg of 5-fluoro-2-(4-fluorophenylamino)-6-(piperidin-1-yl)nicotinamide as a brown solid. LCMS: (M+H)+=333.21. 1H NMR (400 MHz, CDCl3) δ ppm 10.68 (1H, s), 7.52-7.57 (2 H, m), 7.22 (1H, d, J=14.06 Hz), 6.94-7.00 (2H, m), 5.47 (2H, br. s.), 3.64 (4H, d, J=6.15 Hz), 1.62-1.72 (6H, m).

Workup

  1. washwashed with bicarbonate and water
  2. concentrationThe reaction mixture was concentrated
  3. customthe dark crude material was chromatographed
  4. wash(ISCO Companion 40 g silica gel column and eluted with (90:9:1 CH2Cl2:MeOH: NH4OH)t/CH2Cl2 gradient (20-100%))

Sources & evidence

ORD record
ord-056cb50f86cd456faccf043a141dbe51
Source dataset
uspto-grants-2013_11
Patent number
US08586751B2

Reaction notes

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