Diisopropylethylamine → {1-[4-(6-Bromo-8-methyl-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 872306Notes

Reaction equation

HRID 872306 reaction equation
[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1([C:12]2[CH:17]=[CH:16][C:15]([C:18](=O)[CH:19](Br)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:14][CH:13]=2)[CH2:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[NH2:29][C:30]1[C:35]([CH3:36])=[CH:34][C:33]([Br:37])=[CH:32][N:31]=1.C(N(CC)C(C)C)(C)C>CC(O)C>[C:1]([O:5][C:6](=[O:28])[NH:7][C:8]1([C:12]2[CH:13]=[CH:14][C:15]([C:18]3[N:29]=[C:30]4[C:35]([CH3:36])=[CH:34][C:33]([Br:37])=[CH:32][N:31]4[C:19]=3[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[CH:16][CH:17]=2)[CH2:9][CH2:10][CH2:11]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1379342-Amino-5-bromo-3-methylpyridineHCID 86691038tert-Butyl (1-{4-[bromo(phenyl)acetyl]phenyl}cyclobutyl)carbamate

Product 1

HCID 66665128{1-[4-(6-Bromo-8-methyl-3-phenyl-imidazo[1,2-a]pyridin-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterYield 17.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
130 °C

Procedure

1.25 g (2.81 mmol) {1-[4-(2-Bromo-2-phenyl-acetyl)phenyl]-cyclobutyl}-carbamic acid tert.-butyl ester, 631.4 mg (3.38 mmol) 2-amino-5-bromo-3-methyl-pyridine, 2.15 g molecular sieves (4 Å, dried over night at 120° C. in a drying oven), 363.5 mg (2.81 mmol) N,N-diisopropylethylamine in 12 mL 2-propanol (degassed for 15′) in a microwave vial, sealed with a microwave cap, were heated at 130° C. for 17 hours in a heating block. The reaction mixture was sucked off via a glass fibre filter and the filter was washed with dichloromethane. After evaporation to dryness, the residue was redissolved in dichloromethane (200 mL), washed with an 1 M hydrochloric acid (50 mL), saturated sodium bicarbonate (50 mL) and brine (100 mL) and dried (sodium sulfate). After filtration and removal of the solvent the residue was purified by chromatography on silicagel (eluents: hexane/ethyl acetate) yielding 256.7 mg (17.1%) of the title compound.

Workup

  1. customdegassed for 15′) in a microwave vial
  2. customsealed with a microwave
  3. customcap
  4. filtrationfilter
  5. washthe filter was washed with dichloromethane
  6. customAfter evaporation to dryness
  7. dissolutionthe residue was redissolved in dichloromethane (200 mL)
  8. washwashed with an 1 M hydrochloric acid (50 mL), saturated sodium bicarbonate (50 mL) and brine (100 mL)
  9. dry with materialdried (sodium sulfate)
  10. filtrationAfter filtration and removal of the solvent the residue
  11. customwas purified by chromatography on silicagel (eluents: hexane/ethyl acetate)

Sources & evidence

ORD record
ord-e83ab6a75d164371bda3cd6fc72d6af4
Source dataset
uspto-grants-2015_03
Patent number
US08975265B2

Reaction notes

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