Sodium Carbonate → HCID 66744014, compound

HRID 2363986Notes

Reaction equation

HRID 2363986 reaction equation
Br[C:2]1[S:10][C:9]2[C:8](=[O:11])[NH:7][C:6]3([CH2:15][CH2:14][CH2:13][CH2:12]3)[NH:5][C:4]=2[CH:3]=1.CC1(C)C(C)(C)OB([C:24]2[CH:25]=[N:26][NH:27][CH:28]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[NH:26]1[CH:25]=[C:24]([C:2]2[S:10][C:9]3[C:8](=[O:11])[NH:7][C:6]4([CH2:15][CH2:14][CH2:13][CH2:12]4)[NH:5][C:4]=3[CH:3]=2)[CH:28]=[N:27]1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 27740104-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 66744227HCID 66744227, compound

Product 1

HCID 66744014HCID 66744014, compoundYield 50%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 3-amino-5-bromothiophene-2-carboxamide (0.072 g, 0.33 mmol) and p-toluenesulfonic acid monohydrate (0.013 g, 0.066 mmol) in cyclopentanone (2 mL) and acetic acid (1 mL) was stirred at 70° C. for 2 h. Then, the reaction mixture was cooled, carefully poured into sat. NaHCO3 (50 mL), and extracted with 2:1 ethyl acetate/tetrahydrofuran (2×50 mL). The combined organic layers were washed with brine (50 mL), dried over magnesium sulfate, filtered, and concentrated to give crude 6′-bromo-1′H-spiro[cyclopentane-1,2′-thieno[3,2-d]pyrimidin]-4′(3′H)-one as a brown gum (0.174 g), which was used without further purification. A mixture of the crude 6′-bromo-1′H-spiro[cyclopentane-1,2′-thieno[3,2-d]pyrimidin]-4′(3′H)-one (0.172 g), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.349 g, 1.80 mmol), 2 M sodium carbonate (1.2 mL, 2.4 mmol) and 1,1′-bis(diphenylphosphino)ferrocenepalladium (II) dichloride dichloromethane adduct (0.073 g, 0.090 mmol) in 1,4-dioxane (3 mL) was microwave-irradiated at 140° C. for 1 h. Then, the reaction mixture was cooled, and concentrated with silica gel, and the residue was purified by flash chromatography (Combiflash, silica gel, ethyl acetate to 90:10 ethyl acetate/methanol), and purified again by flash chromatography (Combiflash, silica gel, dichloromethane to 90:10 dichloromethane/methanol) to give the title compound (0.045 g, 2 step yield 50%) as a yellow solid:

Workup

  1. customwas used without further purification
  2. customwas microwave-irradiated at 140° C. for 1 h
  3. temperatureThen, the reaction mixture was cooled
  4. concentrationconcentrated with silica gel
  5. customthe residue was purified by flash chromatography (Combiflash, silica gel, ethyl acetate to 90:10 ethyl acetate/methanol)
  6. custompurified again by flash chromatography (Combiflash, silica gel, dichloromethane to 90:10 dichloromethane/methanol)

Sources & evidence

ORD record
ord-3e444123534b4ace8f9ac142398509b1
Source dataset
uspto-grants-2014_04
Patent number
US08691828B2

Reaction notes

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