Potassium Carbonate → HCID 86669253, compound

HRID 2366914Notes

Reaction equation

HRID 2366914 reaction equation
[CH3:1][CH:2]([O:4][C:5](=[O:22])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14](Br)[CH:15]=2)[N:10]([C:18](=[O:20])[CH3:19])[C@@H:9]([CH3:21])[CH2:8]1)[CH3:3].C(=O)([O-])[O-].[K+].[K+].[NH:29]1[C:33](B(O)O)=[CH:32][CH:31]=[N:30]1>C(O)C.C1(C)C=CC=CC=1.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>[CH3:1][CH:2]([O:4][C:5](=[O:22])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:31]3[NH:30][N:29]=[CH:33][CH:32]=3)[CH:15]=2)[N:10]([C:18](=[O:20])[CH3:19])[C@@H:9]([CH3:21])[CH2:8]1)[CH3:3]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 112519791H-Pyrazole-5-boronic acid3×HCID 529350201-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

Product 1

HCID 86669253HCID 86669253, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

1-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (for a preparation see Example 61) (100 mg, 0.271 mmol) was dissolved in ethanol (1 mL) and Toluene (1 mL), mixed with potassium carbonate (74.9 mg, 0.542 mmol), 1H-pyrazol-5-ylboronic acid (36.4 mg, 0.325 mmol, available from Frontier Scientific) followed by tetrakis(triphenylphosphine)palladium(0) (15.65 mg, 0.014 mmol) and refluxed under nitrogen at 90° C. After 21 hours a sample of tetrakis(triphenylphosphine)palladium(0) (15.65 mg, 0.014 mmol) was added to the reaction which was left to stir under nitrogen at the same temperature. Another sample of 1H-pyrazol-5-ylboronic acid (36.4 mg, 0.325 mmol) was added after 171 hours total reaction time and heating and stirring continued. Another sample of 1H-pyrazol-5-ylboronic acid (36.4 mg, 0.325 mmol) was added to the mixture after 345 hours. After 391 hours total reaction time the reaction was partitioned between distilled water (40 mL) and EtOAc (40 mL). The organic and aqueous layers were run off and the latter was extracted twice more using EtOAc (2×40 mL). Organic fractions were combined, washed (brine (80 mL), dried (sodium sulfate), filtered and evaporated to dryness to give a clear, colourless solid (110 mg). This was purified on a 12+M Biotage silica column, eluting with 0 to 100% EtOAc in cyclohexane. Product-containing fractions were evaporated to dryness to give a clear, colourless solid (6 mg).

Workup

  1. waitwas left
  2. temperatureheating
  3. stirringstirring
  4. customAfter 391 hours total reaction time the reaction was partitioned
  5. distillationbetween distilled water (40 mL) and EtOAc (40 mL)
  6. extractionthe latter was extracted twice more
  7. washwashed (brine (80 mL)
  8. dry with materialdried (sodium sulfate)
  9. filtrationfiltered
  10. customevaporated to dryness

Sources & evidence

ORD record
ord-a76da9a923704b429e5cf362ef406f49
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

Loading…