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

HRID 1424112
Notes
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Reaction equation

HRID 1424112 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.[CH2:31]([N:33]1[CH:37]=[C:36](B2OC(C)(C)C(C)(C)O2)[CH:35]=[N:34]1)[CH3:32].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C(OCC)(=O)C>[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:36]5[CH:35]=[N:34][N:33]([CH2:31][CH3:32])[CH:37]=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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 113790451-Ethyl-1H-pyrazole-4-boronic acid, pinacol esterHCID 86712920(8R)-3-[1-(4-Bromophenyl)cyclopropyl]-8-({[t-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

Product 1

HCID 89977493(8R)-8-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-3-{1-[4-(1-ethyl-1H-pyrazol-4-yl)phenyl]cyclopropyl}-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine
Yield 89.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

The compound (600 mg, 1.18 mmol) obtained in Example 52-1), 1-ethyl-1H-pyrazole-4-boronic acid pinacol ester (314 mg, 1.42 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II) dichloride-dichloromethane complex (93 mg, 0.12 mmol), and potassium carbonate (489 mg, 3.54 mmol) were dissolved in a mixed solvent of 1,4-dioxane (4 mL) and water (2 mL), and the mixture was stirred at 90° C. for 5 h. The reaction mixture was cooled to room temperature and then diluted with ethyl acetate (200 mL). The organic layer was washed with saturated aqueous sodium hydrogencarbonate and saturated sodium chloride solution and then dried with anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=40:60 to 100:0) to obtain the title compound (551 mg, 89%) as a white solid.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washThe organic layer was washed with saturated aqueous sodium hydrogencarbonate and saturated sodium chloride solution
  3. dry with materialdried with anhydrous magnesium sulfate
  4. distillationThe solvent was distilled off under reduced pressure
  5. customthe obtained residue was purified by silica gel column chromatography (ethyl acetate:hexane=40:60 to 100:0)

Sources & evidence

ORD record
ord-5a4536a7c3844de4bd9bc4871c30bb99
Source dataset
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08927536B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes