Potassium Carbonate → HCID 90418683, compound

HRID 709974Notes

Reaction equation

HRID 709974 reaction equation
[CH3:1][N:2]1[CH:6]=[C:5](B2OC(C)(C)C(C)(C)O2)[CH:4]=[N:3]1.Cl[C:17]1[CH:22]=[C:21]([O:23][C:24]2[CH:25]=[CH:26][C:27]([C:31]3[C:32]([O:39][CH3:40])=[N:33][C:34]([S:37][CH3:38])=[N:35][CH:36]=3)=[N:28][C:29]=2[CH3:30])[CH:20]=[CH:19][N:18]=1.C([O-])([O-])=O.[K+].[K+]>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.O1CCOCC1.O>[CH3:40][O:39][C:32]1[C:31]([C:27]2[CH:26]=[CH:25][C:24]([O:23][C:21]3[CH:22]=[CH:17][N:18]=[C:19]([C:5]4[CH:4]=[N:3][N:2]([CH3:1])[CH:6]=4)[CH:20]=3)=[C:29]([CH3:30])[N:28]=2)=[CH:36][N:35]=[C:34]([S:37][CH3:38])[N:33]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 90417000HCID 90417000, compound

Product 1

HCID 90418683HCID 90418683, compoundYield 98%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
90 °C

Procedure

A mixture of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.30 g, 1.44 mmol), 5-(5-((2-chloropyridin-4-yl)oxy)-6-methylpyridin-2-yl)-4-methoxy-2-(methylthio)pyrimidine (0.49 g, 1.31 mmol), and K2CO3 (0.54 g, 3.92 mmol) in 5:1 dioxane/water (18 mL) was sparged with Ar, treated with Pd(PPh3)4 (0.15 g, 0.13 mmol), sparged again with Ar and heated at 90° C. for 4 h. The mixture was cooled to RT, treated with satd. NaHCO3, extracted with EtOAc (3×) and the combined organics were dried over Na2SO4, concentrated to dryness and purified via silica gel chromatography (MeOH/DCM) to obtain 4-methoxy-5-(6-methyl-5-((2-(1-methyl-1H-pyrazol-4-yl)pyridin-4-yl)oxy)pyridin-2-yl)-2-(methylthio)pyrimidine (0.54 g, 98%). 1H NMR (400 MHz, DMSO-d6): δ 8.93 (s, 1H), 8.39 (d, J=5.7 Hz, 1H), 8.28 (s, 1H), 7.99 (d, J=0.7 Hz, 1H), 7.88 (d, J=8.5 Hz, 1H), 7.65 (d, J=8.6 Hz, 1H), 7.30 (d, J=2.4 Hz, 1H), 6.66 (dd, J=5.7, 2.4 Hz, 1H), 4.06 (s, 3H), 3.85 (s, 3H), 2.58 (s, 3H), 2.42 (s, 3H); MS (ESI) m/z: 421.1 (M+H+).

Workup

  1. customwas sparged with Ar
  2. customsparged again with Ar
  3. temperatureThe mixture was cooled to RT
  4. additiontreated with satd
  5. extractionNaHCO3, extracted with EtOAc (3×)
  6. dry with materialthe combined organics were dried over Na2SO4
  7. concentrationconcentrated to dryness
  8. custompurified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-b437e8e22bbc41d9bc53dea322e2d30e
Source dataset
uspto-grants-2015_11
Patent number
US09181223B2

Reaction notes

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