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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
Notes
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Reaction equation

HRID 1423981 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]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 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

Product 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
Yield 91%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
140 °C

Procedure

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.

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 (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%)

Sources & evidence

ORD record
ord-b75b113b328b49a4ac5dc1cc60040419
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