1-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole → HCID 46178510, compound

HRID 2088412Notes

Reaction equation

HRID 2088412 reaction equation
Br[C:2]1[N:7]=[C:6]2[N:8]([CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]4[N:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][N:27]5[CH2:32][CH2:31][O:30][CH2:29][CH2:28]5)=[CH:20][N:19]=4)[CH:13]=3)[N:9]=[N:10][C:5]2=[N:4][CH:3]=1.O.O.O.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[CH3:44][N:45]1[CH:49]=[C:48](B2OC(C)(C)C(C)(C)O2)[CH:47]=[N:46]1>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>[CH3:44][N:45]1[CH:49]=[C:48]([C:2]2[N:7]=[C:6]3[N:8]([CH2:11][C:12]4[CH:17]=[CH:16][CH:15]=[C:14]([C:18]5[N:19]=[CH:20][C:21]([O:24][CH2:25][CH2:26][N:27]6[CH2:28][CH2:29][O:30][CH2:31][CH2:32]6)=[CH:22][N:23]=5)[CH:13]=4)[N:9]=[N:10][C:5]3=[N:4][CH:3]=2)[CH:47]=[N:46]1

Participants

6

Reactant 3

HCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 18407952Tripotassium phosphate trihydrateHCID 58289697HCID 58289697, compound

Product 1

HCID 46178510HCID 46178510, compoundYield 35.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Under an argon atmosphere, 225 mg (0.24 mmol) of 6-bromo-1-{3-[5-(2-morpholin-4-ylethoxy)pyrimidin-2-yl]benzyl}-1H-1,2,3-triazolo[4,5-b]pyrazine are dissolved in 5 ml of ethylene glycol dimethyl ether, and 102 mg (0.48 mmol) of tripotassium phosphate trihydrate and 55 mg (0.26 mmol) of 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole are added. The reaction mixture is evacuated and flushed with argon twice. 14 mg (0.02 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. 10 ml of water are added to the reaction mixture, during which an oil precipitates out. This is extracted with dichloromethane and with dichloromethane comprising about 10% of MeOH, the aqueous phase is adjusted to pH 14 using 32% NaOH and again extracted with dichloromethane. The combined organic phases are dried over sodium sulfate and purified by means of preparative HPLC, giving 42 mg of 6-(1-methyl-1H-pyrazol-4-yl)-1-{3-[5-(2-morpholin-4-ylethoxy)pyrimidin-2-yl]benzyl}-1H-1,2,3-triazolo[4,5-b]-pyrazine (“A2”); the product is in the form of the TFA salt; Rt.=2.26 (method A), LCMS: 499 (M+H);

Workup

  1. customThe reaction mixture is evacuated
  2. customflushed with argon twice
  3. customthe mixture is again evacuated
  4. customflushed argon
  5. addition10 ml of water are added to the reaction mixture, during which an oil
  6. customprecipitates out
  7. extractionThis is extracted with dichloromethane and with dichloromethane comprising about 10% of MeOH
  8. extractionagain extracted with dichloromethane
  9. dry with materialThe combined organic phases are dried over sodium sulfate
  10. custompurified by means of preparative HPLC

Sources & evidence

ORD record
ord-ba1f1bc2f4e24638b953171410a1debb
Source dataset
uspto-grants-2013_05
Patent number
US08435986B2

Reaction notes

Loading…