Piperidine → 3,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carboxylic acid (7-chloro-2-oxazol-2-yl-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-amide

HRID 1887837Notes

Reaction equation

HRID 1887837 reaction equation
Cl[C:2]1[CH:34]=[CH:33][C:5]([C:6]([NH:8][CH2:9][C:10]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][C:15]([Cl:21])=[CH:16][CH:17]=3)[N:12]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:11]=2[C:28]2[O:29][CH:30]=[CH:31][N:32]=2)=[O:7])=[CH:4][N:3]=1.[NH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1>CN1C(=O)CCC1>[Cl:21][C:15]1[CH:14]=[C:13]2[C:18]([C:19](=[O:20])[C:10]([CH2:9][NH:8][C:6]([C:5]3[CH:33]=[CH:34][C:2]([N:35]4[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]4)=[N:3][CH:4]=3)=[O:7])=[C:11]([C:28]3[O:29][CH:30]=[CH:31][N:32]=3)[N:12]2[C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)=[CH:17][CH:16]=1

Participants

4

Reactant 2

HCID 8082PiperidineHCID 714866256-chloro-N-((7-chloro-2-(oxazol-2-yl)-4-oxo-1-phenyl-1,4-dihydroquinolin-3-yl)methyl)nicotinamide

Product 1

HCID 712173303,4,5,6-tetrahydro-2H-[1,2']bipyridinyl-5'-carboxylic acid (7-chloro-2-oxazol-2-yl-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-amide

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

In a 20 mL flask, 6-chloro-N-((7-chloro-2-(oxazol-2-yl)-4-oxo-1-phenyl-1,4-dihydroquinolin-3-yl)methyl)nicotinamide (Example I-6) (6 mg, 0.012 mmol) and piperidine (10.4 mg, 0.012 mL, 0.122 mmol) were combined with NMP (0.500 mL) to give a light yellow solution. The reaction mixture was heated at 120° C. for 1.5 hr. After this time, LC/MS showed that the reaction was complete. The reaction mixture was cooled to room temperature, and the solvent was evaporated. The crude product was purified using preparatory reverse-phase HPLC. The product 3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-5′-carboxylic acid (7-chloro-2-oxazol-2-yl-4-oxo-1-phenyl-1,4-dihydro-quinolin-3-ylmethyl)-amide was obtained as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.39 (d, J=2.30 Hz, 1H) 8.31 (d, J=8.59 Hz, 1H) 8.08 (br. s, 1H) 7.96 (d, J=0.80 Hz, 1H) 7.78-7.83 (m, 1H) 7.45-7.54 (m, 4H) 7.38 (d, J=8.20 Hz, 2H) 7.15 (d, J=0.80 Hz, 1H) 6.78-6.85 (m, 1H) 6.71 (d, J=1.95 Hz, 1H) 4.21 (d, J=4.69 Hz, 2H) 3.54-3.61 (m, 4H) 1.45-1.63 (m, 6H). MS calcd. for C30H26ClN5O3 [(M+H)+] 540.2, obsd. 540.1

Workup

  1. customto give a light yellow solution
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customthe solvent was evaporated
  4. customThe crude product was purified

Sources & evidence

ORD record
ord-5d3c0b1d7207455ea45c81d818cb93ab
Source dataset
uspto-grants-2013_08
Patent number
US08501732B2

Reaction notes

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