Picolinic acid → (S)-tert-butyl 4-(4-(1-(cyclopropanecarbonyl)-5-(2, 6-dimethylpyridin-4-yloxy)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

HRID 1051711Notes

Reaction equation

HRID 1051711 reaction equation
[CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[C:11]([OH:34])[C:12]([C:16]4[CH:17]=[N:18][N:19]([CH:21]5[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH2:22]5)[CH:20]=4)=[CH:13][CH:14]=3)[CH2:9][CH2:8][C@@H:7]2[CH3:35])=[O:5])[CH2:3][CH2:2]1.Br[C:37]1[CH:42]=[C:41]([CH3:43])[N:40]=[C:39]([CH3:44])[CH:38]=1.N1C=CC=CC=1C(O)=O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CS(C)=O.[Cu]I.O>[CH:1]1([C:4]([N:6]2[C:15]3[C:10](=[C:11]([O:34][C:37]4[CH:42]=[C:41]([CH3:43])[N:40]=[C:39]([CH3:44])[CH:38]=4)[C:12]([C:16]4[CH:17]=[N:18][N:19]([CH:21]5[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:31])([CH3:33])[CH3:32])=[O:28])[CH2:23][CH2:22]5)[CH:20]=4)=[CH:13][CH:14]=3)[CH2:9][CH2:8][C@@H:7]2[CH3:35])=[O:5])[CH2:3][CH2:2]1

Participants

8

Reactant 4

HCID 1018Picolinic acidHCID 62657Potassium Phosphate, TribasicHCID 130817354-Bromo-2,6-dimethylpyridineHCID 118076350(S)-tert-butyl 4-(4-(1-(cyclopropanecarbonyl)-5-hydroxy-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate

Product 1

HCID 118076088(S)-tert-butyl 4-(4-(1-(cyclopropanecarbonyl)-5-(2, 6-dimethylpyridin-4-yloxy)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylateYield 25%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of (S)-tert-butyl 4-(4-(1-(cyclopropanecarbonyl)-5-hydroxy-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (0.100 g, 0.21 mmol), 4-bromo-2,6-dimethylpyridine (0.077 g, 0.42 mmol), copper (I) iodide (0.004 g, 0.02 mmol), picolinic acid (0.013 g, 0.10 mmol), and potassium phosphate (0.133 g, 0.63 mmol) in DMSO (2 mL) stirred overnight at 90° C. The reaction mixture was cooled to room temperature, poured into water (5 mL), and extracted with ethyl acetate (3×5 mL). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified via column chromatography on silica gel (eluting with 1; 2, ethyl acetate/petroleum ether) to afford (S)-tert-butyl 4-(4-(1-(cyclopropanecarbonyl)-5-(2,6-dimethylpyridin-4-yloxy)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (0.030 g, 25%) as yellow oil. MS (ESI, pos. ion) m/z 586 [M+H]+.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (3×5 mL)
  3. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe residue was purified via column chromatography on silica gel (eluting with 1; 2, ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-85350668c5be48eabd5aa5ca8b146d73
Source dataset
uspto-grants-2016_07
Patent number
US09388161B2

Reaction notes

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