Potassium Phosphate, Tribasic → 4'-{1-[8-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine-3-yl]cyclopropyl}-N,N-dimethylbiphenyl-4-carboxamide

HRID 1423985Notes

Reaction equation

HRID 1423985 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].[CH3:31][N:32]([CH3:44])[C:33]([C:35]1[CH:40]=[CH:39][C:38](B(O)O)=[CH:37][CH:36]=1)=[O:34].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(=O)([O-])O.[Na+]>O1CCOCC1.O.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:38]5[CH:39]=[CH:40][C:35]([C:33]([N:32]([CH3:44])[CH3:31])=[O:34])=[CH:36][CH:37]=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 5

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 516892Sodium BicarbonateHCID 35037674-(Dimethylcarbamoyl)phenylboronic AcidHCID 867128348-({[Tert-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 867128444'-{1-[8-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine-3-yl]cyclopropyl}-N,N-dimethylbiphenyl-4-carboxamideYield 110.3%

Reagents, catalysts & solvents 3

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

Procedure

A solution of the compound (232 mg, 0.5 mmol) obtained in Example 1-2), 4-(N,N-dimethylaminocarbonyl)phenylboronic acid (96 mg, 0.5 mmol), tris(dibenzylideneacetone)dipalladium(0) (23 mg, 0.05 mmol), tricyclohexylphosphine (17 mg, 0.12 mmol), and tripotassium phosphate (186 mg, 0.85 mmol) in dioxane (2 mL) and water (1 mL) was stirred at 140° C. for 2 h under microwave irradiation. The reaction mixture was cooled to room temperature, saturated aqueous sodium hydrogencarbonate was added to the reaction mixture, the mixture was extracted with dichloromethane, and the organic layer was washed with saturated sodium chloride solution and dried with anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 30:70, gradient) to obtain the title compound (318 mg, quant.) as a light yellow oily substance.

Workup

  1. extractionthe mixture was extracted with dichloromethane
  2. washthe organic layer was washed with saturated sodium chloride solution
  3. dry with materialdried with anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customthe residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 30:70, gradient)

Sources & evidence

ORD record
ord-144ed6461ee34af18c461a9d07a66d65
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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