N-bromobutanimide → HCID 178455730, compound

HRID 81211Notes

Reaction equation

HRID 81211 reaction equation
[Br:1]N1C(=O)CCC1=O.[Cl:9][C:10]1[CH:11]=[C:12]([C:16]2[C:21]3[N:22]([CH:25]([C@H:27]4[CH2:32][CH2:31][C@H:30]([CH3:33])[CH2:29][CH2:28]4)[CH3:26])[CH:23]=[N:24][C:20]=3[CH:19]=[C:18]([C:34]#[N:35])[N:17]=2)[CH:13]=[N:14][CH:15]=1>C(Cl)(Cl)Cl.ClCCl>[Br:1][C:23]1[N:22]([CH:25]([C@H:27]2[CH2:32][CH2:31][C@H:30]([CH3:33])[CH2:29][CH2:28]2)[CH3:26])[C:21]2[C:16]([C:12]3[CH:13]=[N:14][CH:15]=[C:10]([Cl:9])[CH:11]=3)=[N:17][C:18]([C:34]#[N:35])=[CH:19][C:20]=2[N:24]=1

Participants

5

Reactant 2

HCID 67184N-bromobutanimideHCID 178455733HCID 178455733, compound

Product 1

HCID 178455730HCID 178455730, compound

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Procedure

N-bromosuccinimide (4.07 g, 22.9 mmol) was added to a room temperature solution of racemic 4-(5-chloropyridin-3-yl)-3-[1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (4.14 g, 7.63 mmol) stirring in degassed chloroform (38 mL). The reaction was heated to reflux for 1.5 hours. The mixture was cooled to room temperature, diluted with dichloromethane, and washed with saturated aqueous sodium thiosulfate (2×) and brine. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-80% ethyl acetate/hexanes, linear gradient) to afford racemic 2-bromo-4-(5-chloropyridin-3-yl)-3-[1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. The racemic material was then purified by chiral supercritical fluid chromatography (Chiralpak IB, 21×250 mm, 25% methanol in CO2) to afford 2-bromo-4-(5-chloropyridin-3-yl)-3-[(1S)-1-(trans-4-methylcyclohexypethyl]-3H-imidazo[4,5-d]pyridine-6-carbonitrile and 2-bromo-4-(5-chloropyridin-3-yl)-3-[(1R)-1-(trans-4-methylcyclohexyl)ethyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. Faster eluting enantiomer 1: MS ESI calc'd. for C21H21BrClN5 [M+H]+ 458. found 458. Slower eluting enantiomer 2: MS ESI calc'd. for C21H21BrClN5 [M+H]+ 458. found 458.

Workup

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 1.5 hours
  3. washwashed with saturated aqueous sodium thiosulfate (2×) and brine
  4. dry with materialThe organic layer was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography (0-80% ethyl acetate/hexanes, linear gradient)

Sources & evidence

ORD record
ord-cb443a66813f47189bcdeef7163237d6
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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