Potassium Phosphate, Tribasic → HCID 58542124, compound

HRID 242004Notes

Reaction equation

HRID 242004 reaction equation
I[C:2]1[CH:28]=[CH:27][C:5]([CH2:6][N:7]2[C:16]3[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=3[C:10]3=[N:17][N:18]([CH:21]4[CH2:26][CH2:25][CH2:24][O:23][CH2:22]4)[C:19](=[O:20])[C:9]3=[N:8]2)=[CH:4][CH:3]=1.[NH:29]1[CH:33]=[CH:32][N:31]=[N:30]1.CN[C@@H]1CCCC[C@H]1NC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CS(C)=O.O.[Cu]I>[O:23]1[CH2:24][CH2:25][CH2:26][CH:21]([N:18]2[C:19](=[O:20])[C:9]3=[N:8][N:7]([CH2:6][C:5]4[CH:27]=[CH:28][C:2]([N:29]5[CH:33]=[CH:32][N:31]=[N:30]5)=[CH:3][CH:4]=4)[C:16]4[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=4[C:10]3=[N:17]2)[CH2:22]1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 46896709HCID 46896709, compoundHCID 178418936HCID 178418936, compound

Product 1

HCID 58542124HCID 58542124, compound

Reagents, catalysts & solvents 3

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

Procedure

(±)-5-(4-Iodobenzyl)-2-(tetrahydro-2H-pyran-3-yl)-2,5-dihydro-3H-pyrazolo[4,3-c]cinnolin-3-one [(Example 45), 25 mg, 0.051 mmol] was dissolved in degassed dimethylsulfoxide (1 mL) and water (0.2 mL), which was treated with copper (I) iodide (3.9 mg, 0.021 mmol, 0.4 equiv), 1,2,3-triazole (4.3 mg, 0.062 mmol, 1.2 equiv), (±)-trans-N,N′-dimethylcyclohexane-1,2-diamine (1.5 mg, 0.0010 mmol, 0.2 equiv) and potassium phosphate (27 mg, 0.15 mmol, 3 equiv). The vessel was sparged under nitrogen, sealed and placed into an oil bath preheated at 100° C. for 5 hours. The mixture was cooled to ambient temperature, poured into sodium bicarbonate (15 mL, aqueous saturated) and extracted with ethyl acetate (3×20 mL). The combined organic extracts were dried with sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography (100:0 to 90:10; dichloromethane:methanol), providing the titled compound as a red solid: 1H-NMR (400 MHz, CDCl3) δ 8.30-8.28 (1H, m), 7.96 (1H, d, J=0.9 Hz), 7.84 (1H, d, J=0.9 Hz), 7.76 (2H, m), 7.74 (2H, d, J=8.6 Hz), 7.58-7.55 (1H, m), 7.46 (2H, d, J=8.4 Hz), 5.87 (2H, s), 4.75-4.67 (1H, m), 4.04 (1H, dd, J=10.7, 1.4 Hz), 3.99 (1H, d, J=11.1 Hz), 3.82 (1H, ap t, J=10.7 Hz), 3.51 (1H, td, J=11.0, 3.3 Hz), 2.29-2.18 (2H, m), 2.12 (1H, br d, J=12.4 Hz), 1.94-1.83 (2H, m) ppm; high resolution mass spectrometry (ES+) m/z 428.1849 [(M+H)+; calculated for C23H22N7O2: 428.1829].

Workup

  1. customThe vessel was sparged under nitrogen
  2. customsealed
  3. customplaced into an oil bath
  4. additionpoured into sodium bicarbonate (15 mL, aqueous saturated)
  5. extractionextracted with ethyl acetate (3×20 mL)
  6. dry with materialThe combined organic extracts were dried with sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by silica gel chromatography (100:0 to 90:10; dichloromethane:methanol)

Sources & evidence

ORD record
ord-d0fd7eca29c146cb9986ef1cc972e67d
Source dataset
uspto-grants-2014_02
Patent number
US08653079B2

Reaction notes

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