Potassium Carbonate → 3-tert-Butyl-1'-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1'H-[1,4]bipyrazolyl-5-ylamine

HRID 2285177Notes

Reaction equation

HRID 2285177 reaction equation
I[C:2]1[CH:3]=[N:4][N:5]([CH2:7][CH2:8][O:9][CH:10]2[CH2:15][CH2:14][CH2:13][CH2:12][O:11]2)[CH:6]=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)[C@@H]1CCCC[C@H]1N>[Cu]I.O.C1(C)C=CC=CC=1>[C:16]([C:20]1[CH:21]=[C:22]([NH2:25])[N:23]([C:2]2[CH:3]=[N:4][N:5]([CH2:7][CH2:8][O:9][CH:10]3[CH2:15][CH2:14][CH2:13][CH2:12][O:11]3)[CH:6]=2)[N:24]=1)([CH3:19])([CH3:18])[CH3:17]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 11275066(1R,2R)-N1,N1-Dimethylcyclohexane-1,2-diamineHCID 593418524-Iodo-1-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethyl)-1H-pyrazoleHCID 178441179HCID 178441179, compound

Product 1

HCID 866871743-tert-Butyl-1'-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1'H-[1,4]bipyrazolyl-5-ylamineYield 81%

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 4-iodo-1-[2-(tetrahydro-pyran-2-yloxy)-ethyl]-1H-pyrazole (for reference procedure see for example WO 2010/139731, which is incorporated herein by reference; 1.54 g, 4.81 mmol), 5-tert-butyl-2H-pyrazol-3-ylamine (668 mg, 4.81 mmol), copper (I) iodide (45 mg, 0.24 mmol) and K2CO3 (1.39 g, 10.1 mmol) was added a solution of toluene (5 mL), previously degassed by using a stream of argon. (R,R)-(−)—N,N-Dimethyl-1,2-cyclohexanediamine (151 μL, 0.96 mmol) was then added and the reaction mixture was heated at 150° C. for 2.5 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 the title compound (1.29 g, 81%). LCMS (Method 1): Rt 2.31 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

Sources & evidence

ORD record
ord-709f9938411b4792b613b224fcaaae09
Source dataset
uspto-grants-2015_09
Patent number
US09145413B2

Reaction notes

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