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Potassium Phosphate, Tribasic → (8R)-8-({[t-Butyl(dimethyl)silyl]oxy}methyl)-8-methyl-3-[1-(4-pyridin-3-ylphenyl)cyclopropyl]-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

HRID 1423981
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HRID 1423981 반응식
[Si:1]([O:8][CH2:9][C@:10]1([CH3:30])[S:16][CH2:15][CH2:14][N:13]2[C:17]([C:20]3([C:23]4[CH:28]=[CH:27][C:26](Cl)=[CH:25][CH:24]=4)[CH2:22][CH2:21]3)=[N:18][N:19]=[C:12]2[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[N:31]1[CH:36]=[CH:35][CH:34]=[C:33](B(O)O)[CH:32]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Si:1]([O:8][CH2:9][C@:10]1([CH3:30])[S:16][CH2:15][CH2:14][N:13]2[C:17]([C:20]3([C:23]4[CH:28]=[CH:27][C:26]([C:33]5[CH:32]=[N:31][CH:36]=[CH:35][CH:34]=5)=[CH:25][CH:24]=4)[CH2:22][CH2:21]3)=[N:18][N:19]=[C:12]2[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]
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9

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HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 27343783-Pyridinylboronic acidHCID 86712840(8R)-8-({[t-Butyl(dimethyl)silyl]oxy}methyl)-3-[1-(4-chlorophenyl)cyclopropyl]-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

생성물 1

HCID 86712841
(8R)-8-({[t-Butyl(dimethyl)silyl]oxy}methyl)-8-methyl-3-[1-(4-pyridin-3-ylphenyl)cyclopropyl]-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine
수율 91%

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 6344Dichloromethane용매HCID 312751,4-Dioxane용매

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온도
140 °C

실험 절차

The compound (460 mg, 0.99 mmol) obtained in Example 4-2), 3-pyridylboronic acid (135 mg, 1.09 mmol), tris(dibenzylideneacetone)dipalladium (45 mg, 0.05 mmol), tricyclohexylphosphine (33 mg, 0.12 mmol), and tripotassium phosphate (370 mg, 1.68 mmol) were dissolved in a mixed solvent of 1,4-dioxane (2 mL) and water (1 mL), and the mixture was stirred at 140° C. for 2 h under microwave irradiation. The reaction mixture was cooled to room temperature, then diluted with methylene chloride (100 mL), and separated into organic and aqueous layers by the addition of saturated aqueous sodium hydrogencarbonate (30 mL). The organic layer was washed with 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 (elution solvent: methanol/ethyl acetate=0% to 30%) to obtain the title compound (455 mg, 91%) in a yellow solid form.

후처리

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customseparated into organic and aqueous layers
  3. additionby the addition of saturated aqueous sodium hydrogencarbonate (30 mL)
  4. washThe organic layer was washed with saturated sodium chloride solution
  5. dry with materialdried with anhydrous magnesium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe obtained residue was purified by silica gel column chromatography (elution solvent: methanol/ethyl acetate=0% to 30%)

출처 및 근거

ORD 기록
ord-b75b113b328b49a4ac5dc1cc60040419
출처 데이터셋
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08927536B2

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