Cesium carbonate → HCID 178434531, compound

HRID 2068624Notes

Reaction equation

HRID 2068624 reaction equation
Br[C:2]1[S:6][CH:5]=[C:4]([C:7]([N:9]2[CH2:15][CH2:14][CH2:13][C:12]([CH3:17])([CH3:16])[CH2:11][CH2:10]2)=[O:8])[CH:3]=1.[CH3:18][C:19]1[C:23](B2OC(C)(C)C(C)(C)O2)=[CH:22][NH:21][N:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>COCCOC.O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[CH3:16][C:12]1([CH3:17])[CH2:13][CH2:14][CH2:15][N:9]([C:7]([C:4]2[CH:3]=[C:2]([C:23]3[C:19]([CH3:18])=[N:20][NH:21][CH:22]=3)[S:6][CH:5]=2)=[O:8])[CH2:10][CH2:11]1

Participants

7

Reactant 3

HCID 10796Cesium carbonate2×HCID 44227299HCID 44227299, compoundHCID 178434487HCID 178434487, compound2×

Product 1

HCID 178434531HCID 178434531, compoundYield 15.3%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst2×HCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

(5-Bromo-thiophen-3-yl)-(4,4-dimethyl-azepan-1-yl)-methanone (0.105 g, 0.33 mmol) together with 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (83 mg, 0.4 mmol), caesium carbonate (0.150 g, 0.46 mmol), and palladium tetrakis(triphenylphosphine) (0.057 g, 0.05 mmol) in DME (3 mL), IMS 1 mL) and water (0.5 mL) was degassed then heated by microwave irradiation to 140° C. for 20 minutes. Further quantities of 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1H-pyrazole (0.035 g), caesium carbonate (0.054 g), and palladium tetrakis(triphenylphosphine) (19 mg) were added and the mixture was heated by microwave irradiation to 140° C. for 20 minutes before diluting with water and extracting with DCM (×3). The organic solution was dried over sodium sulfate, filtered and the solvent evaporated. The residue was purified by chromatography on a silica II cartridge, eluting with 10-60% ethyl acetate in cyclohexane and then was further purified by HPLC using a phenyl hexyl column, eluting with 15%-95% acetonitrile in water (0.1% formic acid) over 20 minutes. The fractions containing the desired product were freeze-dried then taken up as a solution in methanol and dried to give the title compound as a colourless semi-solid (0.016 g). LCMS m/z 318.28 [M+H]+ R.T.=9.29 min (Analytical Method 2).

Workup

  1. temperaturethe mixture was heated by microwave irradiation to 140° C. for 20 minutes
  2. extractionextracting with DCM (×3)
  3. dry with materialThe organic solution was dried over sodium sulfate
  4. filtrationfiltered
  5. customthe solvent evaporated
  6. customThe residue was purified by chromatography on a silica II cartridge
  7. washeluting with 10-60% ethyl acetate in cyclohexane
  8. customwas further purified by HPLC
  9. washeluting with 15%-95% acetonitrile in water (0.1% formic acid) over 20 minutes
  10. additionThe fractions containing the desired product
  11. customwere freeze-dried
  12. customdried

Sources & evidence

ORD record
ord-0a74c1cc9c674ee3815024cccad90efb
Source dataset
uspto-grants-2012_10
Patent number
US08299063B2

Reaction notes

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