Pyrazole → HCID 68153941, compound

HRID 341081

Reaction equation

HRID 341081 reaction equation
[F:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][C:3]=1[CH2:9][N:10]1[C:19]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[C:13]2=[N:20][N:21]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=3[F:30])[C:22](=[O:23])[C:12]2=[CH:11]1.[NH:31]1[CH:35]=[CH:34][CH:33]=[N:32]1.CN[C@@H]1CCCC[C@H]1NC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>[Cu]I.CS(C)=O>[F:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[N:21]1[C:22](=[O:23])[C:12]2=[CH:11][N:10]([CH2:9][C:3]3[CH:4]=[CH:5][C:6]([N:31]4[CH:35]=[CH:34][CH:33]=[N:32]4)=[CH:7][C:2]=3[F:1])[C:19]3[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=3[C:13]2=[N:20]1

Participants

7

Reactant 4

HCID 1048PyrazoleHCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 671125025-[(2-fluoro-4-iodophenyl)methyl]-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazol[4,3-c]quinolin-3-one

Product 1

HCID 68153941HCID 68153941, compound

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

5-[(2-Fluoro-4-iodophenyl)methyl]-2-(2-fluorophenyl)-2,5-dihydro-3H-pyrazol[4,3-c]quinolin-3-one [(Example 187, Step 2), 68 mg, 0.13 mmol], pyrazole (18 mg, 0.26 mmol, 2 equiv) and copper(I) iodide (10 mg, 0.053 mmol, 0.4 equiv) were combined in a sealed tube, to which was added dimethylsulfoxide (1 mL), (±)-trans-N,N′-bismethyl-1,2-cyclohexane diamine (15 mg, 0.11 mmol, 0.8 equiv) and an aqueous (0.2 ml) solution of potassium phosphate (84 mg, 0.40 mmol, 3 equiv). The vessel was flushed with nitrogen, sealed and placed into a preheated oil bath at 100° C. for 1 hour. The mixture was cooled to ambient temperature, poured into water (15 mL) and extracted with chloroform (2×15 mL). The combined organic extracts were washed once with water (5 mL) and brine (5 mL), dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel gradient chromatography (100:0 to 90:10; chloroform:methanol), providing the titled compound: 1H-NMR (400 MHz, d6-DMSO) δ 9.09 (1H, s), 8.54 (1H, d, J=2.6 Hz), 8.21 (1H, dd, J=7.9, 1.5 Hz), 7.82 (1H, dd, J=11.9, 2.1 Hz), 7.73-7.73 (2H, m), 7.68-7.59 (3H, m), 7.55 (1H, t, J=7.6 Hz), 7.49-7.32 (4H, m), 6.56 (1H, dd, J=2.3, 2.0 Hz), 5.82 (2H s) ppm; high resolution mass spectrometry (ES+) m/z 454.1467 [(M+H)+; calculated for C26H18F2N5O: 454.1474].

Workup

  1. customThe vessel was flushed with nitrogen
  2. customsealed
  3. additionpoured into water (15 mL)
  4. extractionextracted with chloroform (2×15 mL)
  5. washThe combined organic extracts were washed once with water (5 mL) and brine (5 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 90:10; chloroform:methanol)

Sources & evidence

ORD record
ord-e5ea697f64c7486c9136aad50841e614
Source dataset
uspto-grants-2014_11
Patent number
US08895580B2

Linked notes

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