Potassium Carbonate → 3-[2-methoxy-4-(1H-pyrazol-4-yl)phenyl]-6-(2,2,6,6-tetramethylpiperidin-4-yl)oxypyridazine

HRID 1027192Notes

Reaction equation

HRID 1027192 reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[N:10][C:11]([O:14][CH:15]3[CH2:20][C:19]([CH3:22])([CH3:21])[NH:18][C:17]([CH3:24])([CH3:23])[CH2:16]3)=[CH:12][CH:13]=2)=[C:4]([O:25][CH3:26])[CH:3]=1.CC1(C)C(C)(C)OB([C:35]2[CH:36]=[N:37][NH:38][CH:39]=2)O1.C([O-])([O-])=O.[K+].[K+]>C(O)C.O.[Pd]>[CH3:26][O:25][C:4]1[CH:3]=[C:2]([C:35]2[CH:36]=[N:37][NH:38][CH:39]=2)[CH:7]=[CH:6][C:5]=1[C:8]1[N:9]=[N:10][C:11]([O:14][CH:15]2[CH2:20][C:19]([CH3:21])([CH3:22])[NH:18][C:17]([CH3:23])([CH3:24])[CH2:16]2)=[CH:12][CH:13]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 867105893-(4-Chloro-2-methoxyphenyl)-6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazine

Product 1

HCID 867105883-[2-methoxy-4-(1H-pyrazol-4-yl)phenyl]-6-(2,2,6,6-tetramethylpiperidin-4-yl)oxypyridazineYield 21%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 19096565Water ethanolSolvent

Conditions

Temperature
160 °C

Procedure

SiliaCat® DPP-Pd (0.37 g, 0.10 mmol) was added to a microwave vial containing a mixture of 3-(4-chloro-2-methoxyphenyl)-6-((2,2,6,6-tetramethylpiperidin-4-yl)oxy)pyridazine (0.36 g, 0.96 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.47 g, 2.4 mmol), and K2CO3 (0.53 g, 3.8 mmol) in ethanol/water (10:1, 6.6 mL). The reaction mixture was sealed, then heated in a microwave reactor at 160° C. for 1 h. After cooling, the reaction was purified by solid phase extraction (5 g SiliaBond Carbonate®, MeOH as eluent). The filtrate was concentrated in vacuo and the resulting residue was purified by flash chromatography (silica gel saturated with Et3N, 2 to 25% MeOH in DCM) to give the desired product (0.08 mg, 21%). [M+H]: 408.4; 1H NMR (400 MHz, DMSO-d6) δ 13.01 (bs, 1H), 8.33 (bs, 1H), 8.05 (bs, 1H), 7.94 (d, J=9.5 Hz, 1H), 7.70 (d, J=8.0 Hz, 1H), 7.38 (d, J=1.5 Hz, 1H), 7.34 (dd, J=8.0, 1.5 Hz, 1H), 7.14 (d, J=9.5 Hz, 1H), 5.57-5.74 (m, 1H), 3.90 (s, 3H), 2.00-2.14 (m, 2H), 1.17-1.31 (m, 8H), 1.11 (s, 6H).

Workup

  1. additioncontaining
  2. customThe reaction mixture was sealed
  3. temperatureAfter cooling
  4. customthe reaction was purified by solid phase extraction (5 g SiliaBond Carbonate®, MeOH as eluent)
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe resulting residue was purified by flash chromatography (silica gel saturated with Et3N, 2 to 25% MeOH in DCM)

Sources & evidence

ORD record
ord-2acdeedf3f2944edb3505e7a7af16d19
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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