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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
ノート
印刷プレビュー

反応式

HRID 1423981 の反応式
[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]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

9

反応物 4

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

生成物 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
収率 91%

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
140 °C

実験手順

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.

後処理

  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%)

出典と根拠

ORDレコード
ord-b75b113b328b49a4ac5dc1cc60040419
出典データセット
uspto-grants-2015_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08927536B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート