Carbon Dioxide → 1-methylethyl ((2S,4R)-1-acetyl-2-methyl-6-{1-[2-(methyloxy)ethyl]-1H-pyrazol-4-yl}-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

HRID 2366964Notes

Reaction equation

HRID 2366964 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].[CH3:23][O:24][CH2:25][CH2:26][N:27]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[N:28]1.C([O-])([O-])=O.[K+].[K+].C(=O)=O>O1CCOCC1.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.C1(C)C=CC=CC=1.CCO>[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:30]3[CH:29]=[N:28][N:27]([CH2:26][CH2:25][O:24][CH3:23])[CH:31]=3)[CH:15]=2)[N:10]([C:18](=[O:20])[CH3:19])[C@@H:9]([CH3:21])[CH2:8]1)[CH3:3]

Participants

9

Reactant 4

HCID 280Carbon DioxideHCID 11430Potassium CarbonateHCID 112304911-(2-Methoxyethyl)-1H-pyrazole-4-boronic acid, pinacol esterHCID 529350201-Methylethyl((cis)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

Product 1

HCID 529350261-methylethyl ((2S,4R)-1-acetyl-2-methyl-6-{1-[2-(methyloxy)ethyl]-1H-pyrazol-4-yl}-1,2,3,4-tetrahydro-4-quinolinyl)carbamateYield 37%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A flask was charged with 1-methylethyl[(2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation see Example 4) (0.185 g, 0.500 mmol), 1-[2-(methyloxy)ethyl]-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (for a preparation see Intermediate 117) (151 mg, 0.600 mmol), K2CO3 (90 mg, 0.650 mmol) and tetrakis(triphenylphosphine)palladium(0) (28.9 mg, 0.025 mmol) then filled with EtOH (1 mL) and toluene (1 mL) and the resulting mixture was stirred at 80° C. for 18 h then cooled to room temperature and concentrated in vacuo. The residue was partitioned between AcOEt (10 mL) and water (10 mL) and the layers were separated. The aqueous layer was extracted with AcOEt and the combined organic phases were washed with brine (25 mL), dried over Na2SO4 and concentrated in vacuo. Purification of the residue using MDAP (modifier: formic acid) gave an oil which was dissolved in 1,4-dioxane, freezed using an acetone bath cooled with solid CO2 and left on a freeze drier for 16 h to give 1-methylethyl((2S,4R)-1-acetyl-2-methyl-6-{1-[2-(methyloxy)ethyl]-1H-pyrazol-4-yl}-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (84.7 mg, 0.204 mmol, 37%) as a white solid. LCMS (method A): Retention time 0.84 min, [M+H]+=415.15

Workup

  1. temperaturethen cooled to room temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between AcOEt (10 mL) and water (10 mL)
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted with AcOEt
  6. washthe combined organic phases were washed with brine (25 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue
  10. customgave an oil which
  11. waitleft on a freeze drier for 16 h

Sources & evidence

ORD record
ord-079dec01b2384ecaa8a6f75c72592bff
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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