Potassium Phosphate, Tribasic → 2-(2-Fluorophenyl)-5-{[5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

HRID 341060Notes

Reaction equation

HRID 341060 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([CH2:8][N:9]2[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]3=[N:19][N:20]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=4[F:29])[C:21](=[O:22])[C:11]3=[CH:10]2)=[N:6][CH:7]=1.[CH3:30][C:31]1[N:32]=[CH:33][NH:34][CH:35]=1.CN[C@@H]1CCCC[C@H]1NC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O.CS(C)=O.[Cu]I>[F:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[N:20]1[C:21](=[O:22])[C:11]2=[CH:10][N:9]([CH2:8][C:5]3[CH:4]=[CH:3][C:2]([N:34]4[CH:35]=[C:31]([CH3:30])[N:32]=[CH:33]4)=[CH:7][N:6]=3)[C:18]3[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=3[C:12]2=[N:19]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 681544925-[(5-Bromopyridin-2-yl)methyl]-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-oneHCID 178418800HCID 178418800, compound

Product 1

HCID 529146072-(2-Fluorophenyl)-5-{[5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]methyl}-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one

Reagents, catalysts & solvents 3

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

Procedure

5-[(5-Bromopyridin-2-yl)methyl]-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazolo[4,3-c]quinolin-3-one [(Example 257, Step 1), 0.13 g, 030 mmol], 4-methyl-1H-imidazole (99 mg, 1.2 mmol, 4 equiv), copper(I) iodide (23 mg, 0.12 mmol, 0.4 equiv), (±)-trans-N,N′-dimethylcyclohexane-1,2-diamine (34 mg, 0.24 mmol, 0.8 equiv) and potassium phosphate (0.19 g, 0.90 mmol, 3 equiv) were combined in water (0.2 mL) and dimethylsulfoxide (1 mL). The mixture was sparged under an atmosphere of nitrogen, the vessel was sealed and placed into a preheated oil bath at 100° C. for 9 hours. The mixture was cooled to ambient temperature, poured into water (25 mL) and extracted with chloroform (2×25 mL). The combined organic extracts were washed with water (20 mL) and brine (20 mL), dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 96:4; chloroform:methanol), providing the titled compound: 1H-NMR (400 MHz, CDCl3) δ 8.70 (1H, d, J=2.7 Hz), 8.55 (1H, s), 8.42 (1H, d, J=7.2 Hz), 7.76 (1H, s), 7.67-7.63 (2H, m), 7.56-7.47 (3H, m), 7.39-7.31 (2H, m), 7.29-7.23 (2H, m), 7.00 (1H, s), 5.59 (2H, s), 2.30 (3H, s) ppm; high resolution mass spectrometry (ES+) m/z 451.1653 [(M+H)+; calculated for C26H20FN6O: 451.1677].

Workup

  1. customThe mixture was sparged under an atmosphere of nitrogen
  2. customthe vessel was sealed
  3. additionpoured into water (25 mL)
  4. extractionextracted with chloroform (2×25 mL)
  5. washThe combined organic extracts were washed with water (20 mL) and brine (20 mL)
  6. dry with materialdried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel gradient chromatography (100:0 to 96:4; chloroform:methanol)

Sources & evidence

ORD record
ord-d5a6aca596bf4d8b9d06feb58c1b72ba
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Reaction notes

Loading…