Potassium Carbonate → 8-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-3-{1-[4-(1H-pyrazol-5-yl)phenyl]cyclopropyl}-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

HRID 1424128Notes

Reaction equation

HRID 1424128 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:11]3[N:15]4[CH2:16][CH2:17][S:18][C:19]([CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])([CH3:21])[CH2:20][C:14]4=[N:13][N:12]=3)[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[NH:31]1[CH:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[N:32]1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.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>[Si:24]([O:23][CH2:22][C:19]1([CH3:21])[S:18][CH2:17][CH2:16][N:15]2[C:11]([C:8]3([C:5]4[CH:6]=[CH:7][C:2]([C:33]5[NH:32][N:31]=[CH:35][CH:34]=5)=[CH:3][CH:4]=4)[CH2:10][CH2:9]3)=[N:12][N:13]=[C:14]2[CH2:20]1)([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 86712858HCID 86712858, compoundHCID 178431094HCID 178431094, compound

Product 1

HCID 867129748-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-3-{1-[4-(1H-pyrazol-5-yl)phenyl]cyclopropyl}-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepineYield 100.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of the compound (300 mg, 0.59 mmol) obtained in Example 16-4), 1H-pyrazole-3-boronic acid pinacol ester (126 mg, 0.65 mmol), tetrakis(triphenylphosphine)palladium(0) (68 mg, 0.06 mmol), and potassium carbonate (163 mg, 1.18 mmol) in 1,2-dimethoxyethane (3 mL) and water (1.5 mL) was stirred at 120° C. for 1 h under microwave irradiation. The reaction mixture was cooled to room temperature, water (3 mL) was added to the reaction mixture, the mixture was extracted with ethyl acetate, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After concentration under reduced pressure, the residue was purified by silica gel chromatography (ethyl acetate:methanol=70:30) to obtain the title compound (295 mg, quant.) in an orange oily form.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washthe organic layer was washed with saturated sodium chloride solution
  3. dry with materialdried with anhydrous sodium sulfate
  4. concentrationAfter concentration under reduced pressure
  5. customthe residue was purified by silica gel chromatography (ethyl acetate:methanol=70:30)

Sources & evidence

ORD record
ord-32d340cfaac8447783429960caccb8e7
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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