Potassium Phosphate, Tribasic → (8S)-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 1423977Notes

Reaction equation

HRID 1423977 reaction equation
[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]

Participants

9

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 27343783-Pyridinylboronic acidHCID 86712837(8S)-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

Product 1

HCID 86712839(8S)-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]thiazepineYield 94.4%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
140 °C

Procedure

The compound (105 mg, 0.23 mmol) obtained in Example 3-2), 3-pyridylboronic acid (31 mg, 0.25 mmol), tris(dibenzylideneacetone)dipalladium (11 mg, 0.01 mmol), tricyclohexylphosphine (8 mg, 0.03 mmol), and tripotassium phosphate (84 mg, 0.38 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 (20 mL), and separated into organic and aqueous layers by the addition of saturated aqueous sodium hydrogencarbonate (10 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 a partially purified product (110 mg) of the title compound in a light yellow solid form.

Workup

  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 (10 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%)

Sources & evidence

ORD record
ord-41aa25584d4e4f95a3b0bea4ca11e588
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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