Tetramethyltin → 4-(4-Methyl-5-isoquinolyl)amino-1-(tert-butoxycarbonyl)piperidine

HRID 10531

Reaction equation

HRID 10531 reaction equation
Br[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH:5]=[N:4][CH:3]=1.[CH3:26][Sn](C)(C)C.C(C1C=C(C)C=C(C(C)(C)C)C=1O)(C)(C)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>[CH3:26][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][C:10]=2[NH:12][CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH:5]=[N:4][CH:3]=1

Participants

6

Reactant 3

HCID 11661TetramethyltinHCID 314042,6-Di-tert-butyl-4-methylphenolHCID 219799724-(4-Bromo-5-isoquinolyl)amino-1-(tert-butoxycarbonyl)piperidine

Product 1

HCID 219798074-(4-Methyl-5-isoquinolyl)amino-1-(tert-butoxycarbonyl)piperidine

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
150 °C

Procedure

A solution of Intermediate 71 (313 mg) in toluene (6 ml) was added with tetrakis(triphenylphosphine)palladium(0) (17.9 mg, Aldrich), tetramethyltin (165 μl, Kanto Chemicals) and 2,6-di-tert-butyl-4-methylphenol (several pellets, Tokyo Kasei Kogyo) and stirred in a sealed tube at 150° C. for 48 hours. The reaction mixture was cooled to room temperature, filtered through Celite and concentrated under reduced pressure. The residue was added with saturated brine (30 ml) and extracted three times with ethyl acetate (30 ml for each time). The organic layers were combined and dried over anhydrous sodium sulfate, and then the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1) to obtain the title compound (61.7 mg).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through Celite
  3. concentrationconcentrated under reduced pressure
  4. additionThe residue was added with saturated brine (30 ml)
  5. extractionextracted three times with ethyl acetate (30 ml for each time)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-2e9115487cd940a38efae8fd5e24df8a
Source dataset
uspto-grants-2006_08
Patent number
US07094789B2

Linked notes

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