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

HRID 630898Notes

Reaction equation

I[C:2]1[CH:3]=[N:4][N:5]([CH2:7][CH2:8][CH2:9][O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][O:12]2)[CH:6]=1.[C:17]([C:21]1[CH:22]=[C:23]([NH2:26])[NH:24][N:25]=1)([CH3:20])([CH3:19])[CH3:18].C([O-])([O-])=O.[K+].[K+].CN[C@@H]1CCCC[C@H]1NC>[Cu]I.O.C1(C)C=CC=CC=1>[C:17]([C:21]1[CH:22]=[C:23]([NH2:26])[N:24]([C:2]2[CH:3]=[N:4][N:5]([CH2:7][CH2:8][CH2:9][O:10][CH:11]3[CH2:16][CH2:15][CH2:14][CH2:13][O:12]3)[CH:6]=2)[N:25]=1)([CH3:20])([CH3:19])[CH3:18]

Participants

Conditions

Temperature: 140 °C

Procedure

To a mixture of intermediate 113a (1.50 g, 4.46 mmol), 5-tert-butyl-2H-pyrazol-3-ylamine (620 mg, 4.46 mmol), copper (I) iodide (42 mg, 0.22 mmol) and K2CO3 (1.29 g, 9.37 mmol) was added a solution of toluene (4.6 mL), previously degassed by using a stream of argon. (R,R)-(−)-N,N′-Dimethyl-1,2-cyclohexanediamine (141 μL, 0.89 mmol) was then added and the reaction mixture was heated at 140° 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 (1.14 g, 73%). LCMS (Method 4): Rt 2.34 min, m/z 348 [MH+].

Workup

custompreviously degassed
customThe crude reaction mixture
extractionextracted with EtOAc (×3)
washThe combined organic layers were washed with brine
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customThe resultant residue was purified by FCC on silica

Sources & evidence

ORD record: ord-89ab88770c214d0f8c355d3ba8b6058f
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09315503B2

Reaction notes

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