Cesium carbonate → HCID 44224458, compound

HRID 1914558Notes

Reaction equation

HRID 1914558 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.C(=O)([O-])[O-].[Cs+].[Cs+].C(OC(=O)C[N:29]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[N:30]1)C>COCCOC.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:32]3[CH:33]=[N:29][NH:30][CH:31]=3)[S:6][CH:5]=2)=[O:8])[CH2:10][CH2:11]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 162183851-(Ethoxycarbonylmethyl)-1H-pyrazole-4-boronic acid pinacol esterHCID 44227299HCID 44227299, compound

Product 1

HCID 44224458HCID 44224458, compoundYield 5%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

(5-Bromo-thiophen-3-yl)-(4,4-dimethyl-azepan-1-yl)-methanone (0.31 g, 0.99 mmol), together with caesium carbonate (0.483 g, 1.49 mmol), [4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrazol-1-yl]-acetic acid ethyl ester (0.28 g, 1.0 mmol) and palladium tetrakis(triphenylphosphine) (114 mg, 0.1 mmol) were taken up in DME (9 mL), IMS (2 mL) and water (1 mL) and the vessel was purged with argon. The reaction mixture was heated by microwave irradiation to 140° C. for 20 minutes and then diluted with water then treated with dilute HCl (pH adjusted to 4) and extracted 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 50 then 100% ethyl acetate in cyclohexane then 5% acetic acid in ethyl acetate. The residue was further purified by HPLC, eluting with 10%-98% acetonitrile in water (0.1% formic acid) and the fractions containing desired product were freeze-dried to give the title compound (0.015 g). LCMS m/z 362.24 [M+H]+ R.T.=8.84 min (Analytical Method 2).

Workup

  1. customIMS (2 mL) and water (1 mL) and the vessel was purged with argon
  2. additiondiluted with water
  3. additionthen treated with dilute HCl (
  4. extractionextracted with DCM (×3)
  5. dry with materialThe organic solution was dried over sodium sulfate
  6. filtrationfiltered
  7. customthe solvent evaporated
  8. customThe residue was purified by chromatography on a silica II cartridge
  9. washeluting with 50
  10. customThe residue was further purified by HPLC
  11. washeluting with 10%-98% acetonitrile in water (0.1% formic acid)
  12. additionthe fractions containing desired product
  13. customwere freeze-dried

Sources & evidence

ORD record
ord-5781a22699b74cf8bd239779931615bc
Source dataset
uspto-grants-2013_12
Patent number
US08614209B2

Reaction notes

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