Triethylamine → Tert-butyl {[6-(5-cyanopent-1-yn-1-yl)-2-isobutyl-4-(4-methylphenyl)quinolin-3-yl]methyl}carbamate

HRID 1986502Notes

Reaction equation

HRID 1986502 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([CH2:17][CH:18]([CH3:20])[CH3:19])[C:11]([CH2:21][NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[C:10]2[C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=1)(=O)=O.[C:39](#[N:45])[CH2:40][CH2:41][CH2:42][C:43]#[CH:44].C(N(CC)CC)C>O1CCCC1.C(OCC)(=O)C.[Cu](I)I>[C:39]([CH2:40][CH2:41][CH2:42][C:43]#[C:44][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[N:13]=[C:12]([CH2:17][CH:18]([CH3:19])[CH3:20])[C:11]([CH2:21][NH:22][C:23](=[O:24])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])=[C:10]2[C:30]1[CH:35]=[CH:34][C:33]([CH3:36])=[CH:32][CH:31]=1)#[N:45]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 1398525-HexynenitrileHCID 510503433-{[(Tert-butoxycarbonyl)amino]methyl}-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl trifluoromethanesulfonate

Product 1

HCID 86605666Tert-butyl {[6-(5-cyanopent-1-yn-1-yl)-2-isobutyl-4-(4-methylphenyl)quinolin-3-yl]methyl}carbamateYield 84.3%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-{[(tert-butoxycarbonyl)amino]methyl}-2-isobutyl-4-(4-methylphenyl)quinolin-6-yl trifluoromethanesulfonate (3.03 g, 6.13 mmol), copper iodide (176 mg, 0.920 mmol) and hex-5-ynenitrile (2.86 g, 30.7 mmol) in tetrahydrofuran (30 ml)-triethylamine (10 ml) was added dichlorobistriphenylphosphinepalladium (431 mg, 0.613 mmol), and the mixture was stirred under an argon atmosphere at 80° C. for 10 min. The reaction mixture was diluted with ethyl acetate, washed with saturated aqueous ammonium chloride solution, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure to give black crystals. The crystals were recrystallized from ethyl acetate-n-hexane to give tert-butyl {[6-(5-cyanopent-1-yn-1-yl)-2-isobutyl-4-(4-methylphenyl)quinolin-3-yl]methyl}carbamate (2.56 g, yield 84%) as white crystals. Subsequently, tert-butyl {[6-(5-cyanopent-1-yn-1-yl)-2-isobutyl-4-(4-methylphenyl)quinolin-3-yl]methyl}carbamate (2.56 g, 5.17 mmol) and 10% palladium-carbon (550 mg) were suspended in a mixed solvent of ethanol (200 ml)-tetrahydrofuran (35 ml) and the mixture was stirred under a hydrogen atmosphere at room temperature for 3.5 hrs. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure to give tert-butyl {[6-(5-cyanopentyl)-2-isobutyl-4-(4-methylphenyl)quinolin-3-yl]methyl}carbamate (2.37 g, yield 92%) as white crystals.

Workup

  1. washwashed with saturated aqueous ammonium chloride solution
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. customto give black crystals
  5. customThe crystals were recrystallized from ethyl acetate-n-hexane

Sources & evidence

ORD record
ord-d264ace2574e46fc9d22aede764dab4d
Source dataset
uspto-grants-2009_06
Patent number
US07547710B2

Reaction notes

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