1,4-Dioxane → tert-Butyl-4-((6-(methylthio)-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamate

HRID 928236Notes

Reaction equation

HRID 928236 reaction equation
Br[C:2]1[C:10]2[C:5](=[N:6][C:7]([S:11][CH3:12])=[N:8][CH:9]=2)[N:4]([CH2:13][C@H:14]2[CH2:19][CH2:18][C@H: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.[C:28]1(B(O)O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.P(=O)([O-])[O-].[K+].[K+].O1CCOCC1>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>[C:23]([O:22][C:21](=[O:27])[NH:20][CH:17]1[CH2:18][CH2:19][CH:14]([CH2:13][N:4]2[C:5]3=[N:6][C:7]([S:11][CH3:12])=[N:8][CH:9]=[C:10]3[C:2]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[N:3]2)[CH2:15][CH2:16]1)([CH3:26])([CH3:25])[CH3:24]

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 66827Phenylboronic AcidHCID 178503372HCID 178503372, compoundHCID 178527066HCID 178527066, compound

Product 1

HCID 67470951tert-Butyl-4-((6-(methylthio)-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamateYield 88.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×

Conditions

Temperature
150 °C

Procedure

A microwave tube was charged with tert-butyl trans-4-((3-bromo-6-(methylthio)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamate (0.046 g, 0.1 mmol), phenylboronic acid (0.037 g, 0.3 mmol), potassium phosphonate (0.063 g, 0.3 mmol), tetrakis(triphenylphosphine)palladium (0.012 g, 0.01 mmol), dioxane (2 mL) and water (0.5 mL). The mixture was heated in microwave at 150° C. for 10 min. The reaction mixture was poured into water. The aqueous layer was extracted with Et2O (3×). The combined organic layers were dried (Na2SO4), concentrated, and purified by Isco to give tert-Butyl-4-((6-(methylthio)-3-phenyl-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)cyclohexylcarbamate (0.040 g, 88%) as a white solid. MS m/z 454.3 [M+H]+.

Workup

  1. extractionThe aqueous layer was extracted with Et2O (3×)
  2. dry with materialThe combined organic layers were dried (Na2SO4)
  3. concentrationconcentrated
  4. custompurified by Isco

Sources & evidence

ORD record
ord-21c1fbe2ba244bcf883044ca7e4858bb
Source dataset
uspto-grants-2016_03
Patent number
US09290499B2

Reaction notes

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