1,4-Dioxane → tert-butyl 4-((6-(methylamino)-3-p-tolyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamate

HRID 928230Notes

Reaction equation

HRID 928230 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([NH:11][CH3:12])=[N:8][CH:9]=2)[N:4]([CH2:13][CH:14]2[CH2:19][CH2:18][CH:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:16][CH2:15]2)[N:3]=1.B(O)(O)[C:29]1[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=1.P(=O)([O-])[O-].[K+].[K+].O1CCOCC1>CCOC(C)=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.O>[CH3:12][NH:11][C:7]1[N:6]=[C:5]2[N:4]([CH2:13][CH:14]3[CH2:19][CH2:18][CH:17]([NH:20][C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH2:16][CH2:15]3)[N:3]=[C:2]([C:29]3[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=3)[C:10]2=[CH:9][N:8]=1

Participants

8

Reactant 4

HCID 312751,4-DioxaneHCID 79799Tolylboronic acidHCID 68212722tert-butyl 4-((3-bromo-6-(methylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamateHCID 178527066HCID 178527066, compound

Product 1

HCID 68212721tert-butyl 4-((6-(methylamino)-3-p-tolyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamateYield 89%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A 30 mL microwave tube was charged with tert-butyl 4-((3-bromo-6-(methylamino)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamate (0.070 g, 0.16 mmol), p-tolylboronic acid (0.065 g, 0.48 mmol), potassium phosphonate (0.10 g, 0.48 mmol), tetrakis(triphenylphosphine)palladium (0.018 g, 0.016 mmol), dioxane (2 mL) and water (0.5 mL). After stirring for 5 min, the reaction was heat at 150° C. for 10 min in microwave. The reaction was diluted with EtOAc and washed with water. The aqueous layer was extracted with EtOAc (3×). The combined organic layers were dried (Na2SO4), concentrated, and purified by Isco to provide tert-butyl 4-((6-(methylamino)-3-p-tolyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamate (0.064 g, 89%) as a white solid.

Workup

  1. washwashed with water
  2. extractionThe aqueous layer was extracted with EtOAc (3×)
  3. dry with materialThe combined organic layers were dried (Na2SO4)
  4. concentrationconcentrated
  5. custompurified by Isco

Sources & evidence

ORD record
ord-21825bf56d444262a58e24a131f92a88
Source dataset
uspto-grants-2016_03
Patent number
US09290499B2

Reaction notes

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