1-(2-Morpholinoethyl)-1H-pyrazole-4-boronic acid pinacol ester → (3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}phenyl)methanol

HRID 2088411Notes

Reaction equation

HRID 2088411 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([C:8]2[CH:9]=[C:10]([CH2:14][OH:15])[CH:11]=[CH:12][CH:13]=2)=[N:6][CH:7]=1.CC1(C)C(C)(C)OB([C:24]2[CH:25]=[N:26][N:27]([CH2:29][CH2:30][N:31]3[CH2:36][CH2:35][O:34][CH2:33][CH2:32]3)[CH:28]=2)O1.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>COCCOC.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>[N:31]1([CH2:30][CH2:29][N:27]2[CH:28]=[C:24]([C:2]3[CH:3]=[N:4][C:5]([C:8]4[CH:9]=[C:10]([CH2:14][OH:15])[CH:11]=[CH:12][CH:13]=4)=[N:6][CH:7]=3)[CH:25]=[N:26]2)[CH2:32][CH2:33][O:34][CH2:35][CH2:36]1

Participants

6

Reactant 3

HCID 177499241-(2-Morpholinoethyl)-1H-pyrazole-4-boronic acid pinacol esterHCID 18407952Tripotassium phosphate trihydrateHCID 59484879(3-(5-Bromopyrimidin-2-yl)phenyl)methanol

Product 1

HCID 58289705(3-{5-[1-(2-morpholin-4-ylethyl)-1H-pyrazol-4-yl]pyrimidin-2-yl}phenyl)methanol

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Under an argon atmosphere, 2.82 g (10 mmol) of [3-(5-bromopyrimidin-2-yl)-phenyl]methanol are dissolved in 100 ml of ethylene glycol dimethyl ether, 3.38 g (10 mmol) of 4-{2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazol-1-yl]ethyl}morpholine and 4.25 g (20 mmol) of tripotassium phosphate trihydrate are added. The reaction mixture is evacuated twice and flushed with argon. 840 mg (1.2 mmol) of bis(triphenylphosphine)palladium(II) chloride are added, the mixture is again evacuated and flushed argon. The reaction mixture is stirred at 80° C. for 16 hours. The reaction mixture is diluted with dichloromethane and water and filtered through Celite. The organic phase is separated off, washed with water again, the organic phase is dried over sodium sulfate and evaporated to dryness. The residue is recrystallised from isopropanol; yield: 2.74 g, LCMS: 366 (M+H).

Workup

  1. customThe reaction mixture is evacuated twice
  2. customflushed with argon
  3. customthe mixture is again evacuated
  4. customflushed argon
  5. additionThe reaction mixture is diluted with dichloromethane and water
  6. filtrationfiltered through Celite
  7. customThe organic phase is separated off
  8. washwashed with water again
  9. dry with materialthe organic phase is dried over sodium sulfate
  10. customevaporated to dryness
  11. customThe residue is recrystallised from isopropanol

Sources & evidence

ORD record
ord-686f3b7714d54d8aa249749e8d5ed013
Source dataset
uspto-grants-2013_05
Patent number
US08435986B2

Reaction notes

Loading…