Ethyl Acetate → 6-cyano-8-(cyclohexylmethoxy)-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide

HRID 64461

Reaction equation

Br[C:2]1[CH:3]=[C:4]([O:24][CH2:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)[C:5]2[N:6]([C:8]([C:12]([NH:14][C@H:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:16][OH:17])=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1.C(OCC)(=O)C.[CH3:38][N:39]1CCCC1=O>[C-]#N.[Zn+2].[C-]#N.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC(P([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Fe]>[C:38]([C:2]1[CH:3]=[C:4]([O:24][CH2:25][CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)[C:5]2[N:6]([C:8]([C:12]([NH:14][C@H:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH2:16][OH:17])=[O:13])=[C:9]([CH3:11])[N:10]=2)[CH:7]=1)#[N:39]

Participants

Conditions

Temperature: 180 °C

Procedure

To a solution of 90 mg of 6-bromo-8-(cyclohexylmethoxy)-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide in 1.8 ml of N-methyl-2-pyrrolidone were added 54 mg of zinc cyanide and 27 mg of [1,1-bis(diphenylphosphino)ferrocene]dichloropalladium (II), followed by stirring at 180° C. for 30 minutes under a condition for microwave irradiation. To the reaction mixture was added 46 mg of zinc cyanide, followed by further stirring at 180° C. for 30 minutes under a condition for microwave irradiation. To the reaction mixture were added ethyl acetate and a saturated aqueous sodium hydrogen carbonate solution, followed by filtration through Celite. A layer separation operation of the obtained filtrate was carried out, the organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 7 mg of 6-cyano-8-(cyclohexylmethoxy)-N-[(1R)-2-hydroxy-1-phenylethyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide.

Workup

stirringby further stirring at 180° C. for 30 minutes under a condition for microwave irradiation
filtrationa saturated aqueous sodium hydrogen carbonate solution, followed by filtration through Celite
customA layer separation operation of the obtained filtrate
washthe organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution and saturated brine
dry with materialdried over anhydrous sodium sulfate
customthe solvent was evaporated under reduced pressure
customThe obtained residue was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-d606294be9834a4594300d4bcd62aef9
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09447090B2

Linked notes

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