Potassium Carbonate → HCID 90416623, compound

HRID 709976Notes

Reaction equation

HRID 709976 reaction equation
Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:10]=[CH:11][C:12]([C:16]3[C:17]([O:25][CH3:26])=[N:18][C:19]([NH:22][CH2:23][CH3:24])=[N:20][CH:21]=3)=[N:13][C:14]=2[CH3:15])[CH:5]=[CH:4][N:3]=1.[CH3:27][N:28]1[CH:32]=[C:31](B2OC(C)(C)C(C)(C)O2)[CH:30]=[N:29]1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:23]([NH:22][C:19]1[N:18]=[C:17]([O:25][CH3:26])[C:16]([C:12]2[CH:11]=[CH:10][C:9]([O:8][C:6]3[CH:5]=[CH:4][N:3]=[C:2]([C:31]4[CH:30]=[N:29][N:28]([CH3:27])[CH:32]=4)[CH:7]=3)=[C:14]([CH3:15])[N:13]=2)=[CH:21][N:20]=1)[CH3:24]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 90416638HCID 90416638, compound

Product 1

HCID 90416623HCID 90416623, compoundYield 71%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of Example C1 (0.12 g, 0.26 mmol) and 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.070 g, 0.35 mmol) in dioxane (4 mL) was sparged with Ar, treated with a solution of K2CO3 (0.07 g, 0.51 mmol) in water (1 mL), Pd(PPh3)4 (0.03 g, 0.026 mmol) and heated at 90° C. for 2 h. The mixture was cooled to RT, diluted with water, extracted with EtOAc (2×) and the combined organics were washed with brine, dried over Na2SO4, concentrated to dryness and purified by column chromatography (MeOH/DCM) to afford N-ethyl-4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)pyrimidin-2-amine as a white solid (77 mg, 71%). 1H NMR (400 MHz, DMSO-d6): δ 8.74 (s, 1H), 8.36 (d, J=5.7 Hz, 1H), 8.26 (s, 1H), 7.97 (d, J=0.7 Hz, 1H), 7.76 (d, J=8.5 Hz, 1H), 7.55 (d, J=8.6 Hz, 1H), 7.36 (br s, 1H), 7.25 (d, J=2.4 Hz, 1H), 6.61 (dd, J=5.7, 2.4 Hz, 1H), 3.96 (s, 3H), 3.84 (s, 3H), 3.40-3.30 (m, 2H), 2.37 (s, 3H), 1.14 (br m, 3H); MS (ESI) m/z: 418.2 (M+H+).

Workup

  1. temperatureThe mixture was cooled to RT
  2. extractionextracted with EtOAc (2×)
  3. washthe combined organics were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to dryness
  6. custompurified by column chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-1d0847b67cf84b699ac6253fc842f16f
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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