Hydrochloric Acid → HCID 86712888, compound

HRID 1424037Notes

Reaction equation

HRID 1424037 reaction equation
[Si]([O:8][CH2:9][C:10]1([CH3:38])[S:16][CH2:15][CH2:14][N:13]2[C:17]([C:20]3([C:23]4[CH:28]=[CH:27][C:26](B5OC(C)(C)C(C)(C)O5)=[CH:25][CH:24]=4)[CH2:22][CH2:21]3)=[N:18][N:19]=[C:12]2[CH2:11]1)(C(C)(C)C)(C)C.Cl[C:40]1[N:47]=[CH:46][CH:45]=[CH:44][C:41]=1[C:42]#[N:43].C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])O.[Na+].Cl>C(COC)OC.O.CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:8][CH2:9][C:10]1([CH3:38])[S:16][CH2:15][CH2:14][N:13]2[C:17]([C:20]3([C:23]4[CH:24]=[CH:25][C:26]([C:40]5[N:47]=[CH:46][CH:45]=[CH:44][C:41]=5[C:42]#[N:43])=[CH:27][CH:28]=4)[CH2:22][CH2:21]3)=[N:18][N:19]=[C:12]2[CH2:11]1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 810792-ChloronicotinonitrileHCID 516892Sodium BicarbonateHCID 867128608-({[Tert-butyl(dimethyl)silyl]oxy}methyl)-8-methyl-3-{1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]cyclopropyl}-5,6,8,9-tetrahydro[1,2,4]triazolo[4,3-d][1,4]thiazepine

Product 1

HCID 86712888HCID 86712888, compoundYield 82%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of the compound (555 mg, 1.0 mmol) obtained in Example 16-5), 2-chloronicotinonitrile (290 mg, 1.5 mmol), tetrakis(triphenylphosphine)palladium(0) (231 mg, 0.2 mmol), and potassium carbonate (276 mg, 2 mmol) in dimethoxyethane (4 mL) and water (1 mL) was stirred at 130° C. for 1.5 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 partially purified by silica gel chromatography (Isco Combiflash, 40 g, methanol:ethyl acetate=0:100 to 20:80, gradient). A solution of this partially purified product (444 mg, 0.83 mmol) and 4 M hydrochloric acid (1,4-dioxane solution, 1 mL) in methanol (4 mL) was stirred at room temperature for 5 h. The reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate was added to the residue, 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 40:60, gradient) to obtain the title compound (286 mg, 82%) as a colorless solid.

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 partially purified by silica gel chromatography (Isco Combiflash, 40 g, methanol:ethyl acetate=0:100 to 20:80, gradient)
  7. concentrationThe reaction mixture was concentrated under reduced pressure, saturated aqueous sodium hydrogencarbonate
  8. additionwas added to the residue
  9. extractionthe mixture was extracted with dichloromethane
  10. washthe organic layer was washed with saturated sodium chloride solution
  11. dry with materialdried with anhydrous sodium sulfate
  12. filtrationAfter filtration
  13. concentrationthe filtrate was concentrated under reduced pressure
  14. customthe residue was purified by silica gel chromatography (Isco Combiflash, 12 g, methanol:ethyl acetate=0:100 to 40:60, gradient)

Sources & evidence

ORD record
ord-5901de6df2b74a5987f8331be0e0c240
Source dataset
uspto-grants-2015_01
Patent number
US08927536B2

Reaction notes

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