4-Methylpyrazole → HCID 71233130, compound

HRID 2409892Notes

Reaction equation

HRID 2409892 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH2:11][C@H:10]([NH:14][C@@H:15]3[CH2:20][CH2:19][CH2:18][CH2:17][C@H:16]3[NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:9]2)=[CH:4][CH:3]=1.[CH3:29][C:30]1[CH:31]=[N:32][NH:33][CH:34]=1.CN[C@@H]1CCCC[C@H]1NC.C([O-])([O-])=O.[K+].[K+]>[Cu]I>[CH3:29][C:30]1[CH:31]=[N:32][N:33]([C:2]2[CH:7]=[CH:6][C:5]([N:8]3[CH2:13][CH2:12][CH2:11][C@H:10]([NH:14][C@@H:15]4[CH2:20][CH2:19][CH2:18][CH2:17][C@H:16]4[NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH2:9]3)=[CH:4][CH:3]=2)[CH:34]=1

Participants

6

Reactant 4

HCID 34064-MethylpyrazoleHCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 86690342HCID 86690342, compound

Product 1

HCID 71233130HCID 71233130, compoundYield 63.3%

Reagents, catalysts & solvents 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst

Conditions

Temperature
100 °C

Procedure

To a sealed tube was added tert-butyl (1R,2R)-2-((S)-1-(4-iodophenyl)piperidin-3-ylamino)cyclohexylcarbamate (150 mg, 0.300 mmol), 4-methyl-1H-pyrazole (29.6 mg, 0.360 mmol), (1R,2R)—N1,N2-dimethylcyclohexane-1,2-diamine (8.54 mg, 0.060 mmol), K2CO3 (87 mg, 0.631 mmol) and copper(I) iodide (5.72 mg, 0.030 mmol). The reaction was bubbled with argon for 2 min. The reaction vessel was sealed and the reaction was stirred at 100° C. for 16 hrs. After this time, the reaction was cooled to rt and diluted with water. The layers were separated and aqueous solution was extracted with EtOAc (2×30 ml). The combined organic layers were washed with saturated aqueous NaCl (30 ml), dried over Na2SO4, filtered and concentrated. The resulting residue was purified using silica gel chromatography (ISCO system) eluting with a gradient of 20-100% EtOAc/Hex to give tert-butyl (1R,2R)-2-((S)-1-(4-(4-methyl-1H-pyrazol-1-yl)phenyl)piperidin-3-ylamino)cyclohexylcarbamate (86 mg, 0.190 mmol, 63.1% yield). Anal. Calcd. for C26H39N5O2 m/z 453.5, found: 454.4 (M+H)+.

Workup

  1. customThe reaction was bubbled with argon for 2 min
  2. customThe reaction vessel was sealed
  3. temperatureAfter this time, the reaction was cooled to rt
  4. additiondiluted with water
  5. customThe layers were separated
  6. extractionaqueous solution was extracted with EtOAc (2×30 ml)
  7. washThe combined organic layers were washed with saturated aqueous NaCl (30 ml)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe resulting residue was purified
  12. washeluting with a gradient of 20-100% EtOAc/Hex

Sources & evidence

ORD record
ord-a8826aac0bb247ebb959c75a285b9dbb
Source dataset
uspto-grants-2014_08
Patent number
US08815909B2

Reaction notes

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