Diethyl Ether → HCID 89924554, compound

HRID 1505677Notes

Reaction equation

HRID 1505677 reaction equation
C(OC([N:8]1[CH:12]=[C:11](B2OC(C)(C)C(C)(C)O2)[CH:10]=[N:9]1)=O)(C)(C)C.Br[C:23]1[CH:24]=[N:25][C:26]([C:29]2[CH:30]=[C:31]([CH:33]=[CH:34][CH:35]=2)[NH2:32])=[N:27][CH:28]=1.C(=O)([O-])[O-].[K+].[K+].CCOCC>O1CCOCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH:9]1[CH:10]=[C:11]([C:23]2[CH:28]=[N:27][C:26]([C:29]3[CH:30]=[C:31]([NH2:32])[CH:33]=[CH:34][CH:35]=3)=[N:25][CH:24]=2)[CH:12]=[N:8]1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 11430Potassium CarbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 63318778HCID 63318778, compound2×

Product 1

HCID 89924554HCID 89924554, compoundYield 87%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazole-1-carboxylic acid tert-butyl ester (20.7 g; 70.4 mmol; 1.0 eq.), 3-(5-Bromo-pyrimidin-2-yl)-phenylamine (intermediate 4, 17.6 g; 70.4 mmol; 1.0 eq.), bis(triphenylphosphine)palladium(II) chloride (4.94 g; 7.04 mmol; 0.10 eq.) and potassium carbonate (14.6 g; 105 mmol; 1.5 eq.) were suspended in dioxane (540 mL) and water (273 mL). The reaction mixture was then heated at 90° C. for 16 h. It was filtered through Celite and the filtrate was extracted with EtOAc. Organic phase was washed with brine, dried over magnesium sulfate, filtered and concentrated. The gum obtained was then triturated Et2O (100 mL). The resulting solid was filtered off and dried under high vacuum to give the title compound as a beige solid (14 g, 87%). 1H NMR (300 MHz, DMSO-d6) δ 13.21 (brs, 1H), 9.12 (s, 2H), 8.44 (m, 1H), 8.14 (m, 1H), 7.67 (t, J=2.0 Hz, 1H), 7.57-7.54 (m, 1H), 7.14 (t, J=7.8 Hz, 1H), 5.25 (s, 2H), 6.68 (ddd, J=7.8 Hz, 2.0 Hz, 1.0 Hz, 1H). HPLC (Condition A): Rt 1.24 min (purity 72.1%). MS (ESI+): 238.2.

Workup

  1. filtrationIt was filtered through Celite
  2. extractionthe filtrate was extracted with EtOAc
  3. washOrganic phase was washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe gum obtained
  8. filtrationThe resulting solid was filtered off
  9. customdried under high vacuum

Sources & evidence

ORD record
ord-22df07bd6305498187c1291b9280d617
Source dataset
uspto-grants-2015_12
Patent number
US09216991B2

Reaction notes

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