1,4-Dioxane → HCID 67394324, compound

HRID 1045779Notes

Reaction equation

HRID 1045779 reaction equation
Br[C:2]1[C:3]2[N:4](N=N[N:23]=2)[C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[S:24]1[CH:28]=[CH:27][CH:26]=[C:25]1B(O)O.CC(C)([O-])C.[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>[NH2:23][C:3]1[C:2]([C:25]2[S:24][CH:28]=[CH:27][CH:26]=2)=[CH:7][N:6]=[C:5]([N:8]2[CH2:13][CH2:12][N:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10][CH2:9]2)[N:4]=1

Participants

7

Reactant 4

HCID 312751,4-DioxaneHCID 27339602-Thiopheneboronic acidHCID 23665647Potassium tert-butoxideHCID 58447051HCID 58447051, compound

Product 1

HCID 67394324HCID 67394324, compoundYield 8.7%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A 500 mL round bottom flask was charged with tert-butyl 4-(8-bromotetrazolo[1,5-c]pyrimidin-5-yl)piperazine-1-carboxylate (5.5 g, 14.3 mmol), thiophene-2-boronic acid (2.5 g, 21.5 mmol), tetrakis(triphenylphosphine)palladium(0) (2.0 g, 1.43 mmol), potassium tert-butoxide (2.4 g, 21.5 mmol), 1,4-dioxane (200 mL) and water (50 mL). After the air was purged by bubbling N2 into the solution, the resulting mixture was stirred at 80° C. under N2 for 10 h. Work-up: the reaction mixture was diluted with 0.1 M HCl (20 mL) and washed with EtOAc (150 mL×3). The aqueous layer was then basified with solid NaHCO3 and extracted with CH2Cl2 (150 mL×3). The combined CH2Cl2 layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with 1-10% MeOH in CH2Cl2 to afford 0.70 g (12%) of the product, and 0.45 g (8.7%) of tert-butyl 4-(4-amino-5-(thiophen-2-yl)pyrimidin-2-yl)piperazine-1-carboxylate.

Workup

  1. customAfter the air was purged
  2. customby bubbling N2 into the solution
  3. additionthe reaction mixture was diluted with 0.1 M HCl (20 mL)
  4. washwashed with EtOAc (150 mL×3)
  5. extractionextracted with CH2Cl2 (150 mL×3)
  6. dry with materialThe combined CH2Cl2 layers were dried over anhydrous Na2SO4
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel with 1-10% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-2bb17e687a544a61807092e219128361
Source dataset
uspto-grants-2013_10
Patent number
US08569300B2

Reaction notes

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