Potassium Carbonate → 5-tert-Butyl-2-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-imidazol-4-yl}-2H-pyrazol-3-ylamine

HRID 630908Notes

Reaction equation

HRID 630908 reaction equation
I[C:2]1[N:6]([CH2:7][CH2:8][O:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][O:11]2)[CH:5]=[N:4][CH:3]=1.[C:16]([C:20]1[CH:21]=[C:22]([NH2:25])[NH:23][N:24]=1)([CH3:19])([CH3:18])[CH3:17].C([O-])([O-])=O.[K+].[K+].CN[C@@H]1CCCC[C@H]1NC>[Cu]I.O.C1(C)C=CC=CC=1>[C:16]([C:20]1[CH:21]=[C:22]([NH2:25])[N:23]([C:3]2[N:4]=[CH:5][N:6]([CH2:7][CH2:8][O:9][CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][O:11]3)[CH:2]=2)[N:24]=1)([CH3:19])([CH3:18])[CH3:17]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamineHCID 866871945-iodo-1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-imidazole2×HCID 178441179HCID 178441179, compound

Product 1

HCID 866871935-tert-Butyl-2-{1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-imidazol-4-yl}-2H-pyrazol-3-ylamineYield 35.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
150 °C

Procedure

To a mixture of Intermediate 119a (1.50 g, 4.66 mmol), 5-tert-butyl-2H-pyrazol-3-ylamine (648 mg, 4.66 mmol), copper(I)iodide (44 mg, 0.23 mmol) and K2CO3 (1.35 g, 9.78 mmol) was added a solution of toluene (10 mL), previously degassed by using a stream of argon. (R,R)-(−)-N,N′-Dimethyl-1,2-cyclohexanediamine (147 μL, 0.93 mmol) was then added and the reaction mixture was heated at 150° C. for 3 h under microwave irradiation. The crude reaction mixture was poured into water and extracted with EtOAc (×3). The combined organic layers were washed with brine, dried (MgSO4) and concentrated in vacuo. The resultant residue was purified by FCC on silica, using a gradient of 0-100% EtOAc in cyclohexane, to give a product consisting of the title compound (550 mg) in mixture with the un-reacted 5-iodo-1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-imidazole isomer. LCMS (Method 4): Rt 2.32 min, m/z 334 [MH+].

Workup

  1. custompreviously degassed
  2. customThe crude reaction mixture
  3. extractionextracted with EtOAc (×3)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo
  7. customThe resultant residue was purified by FCC on silica
  8. customto give a product

Sources & evidence

ORD record
ord-0f8839c2a8a04dbc83f1d8ca627ca3fe
Source dataset
uspto-grants-2016_04
Patent number
US09315503B2

Reaction notes

Loading…