1,3-Dibromo-5,5-dimethylhydantoin → HCID 178467426, compound

HRID 81286Notes

Reaction equation

HRID 81286 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([O:8][CH:9]([CH:11]2[CH2:14][CH2:13][CH2:12]2)[CH3:10])[C:5]2[N:15]([CH2:18][C@H:19]3[CH2:24][CH2:23][C@H:22]([CH3:25])[CH2:21][CH2:20]3)[CH:16]=[N:17][C:4]=2[CH:3]=1.[Cl-].[Li+].CC1(C)CCCC(C)(C)N1[Mg]Cl.[Br:40]N1C(C)(C)C(=O)N(Br)C1=O>C1COCC1>[Br:40][C:16]1[N:15]([CH2:18][C@H:19]2[CH2:20][CH2:21][C@H:22]([CH3:25])[CH2:23][CH2:24]2)[C:5]2[C:6]([O:8][CH:9]([CH:11]3[CH2:12][CH2:13][CH2:14]3)[CH3:10])=[N:7][C:2]([Cl:1])=[CH:3][C:4]=2[N:17]=1

Participants

5

Reactant 3

HCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 178424953HCID 178424953, compoundHCID 178467428HCID 178467428, compound

Product 1

HCID 178467426HCID 178467426, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred solution of 6-chloro-4-(1-cyclobutylethoxy)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine (3.5 g, 11.73 mmol) in THF (20 mL) was added 2,2,6,6-tetramethylpiperidinyl magnesium chloride lithium chloride complex (1.0 M in THF/Toluene, 29.8 mL, 29.84 mmol) at −78° C. The resulting solution was stirred 2.5 hours and then 1,3 dibromo-5,5 dimethyl hydantoin (8.5 g, 29.84 mmol) in THF (20 mL) was added dropwise at −78° C. The reaction was stirred for 30 minutes then slowly warmed to room temperature over a period of 2 hours. The reaction was quenched with saturated NH4Cl solution (50 mL) at 0° C. and extracted with EtOAc (2×20 mL). The combined organic extracts were washed with water (20 mL) and brine (20 mL), dried over anhydrous Na2SO4, filtered, and concentrated. The residue was purified by silica gel chromatography (eluting with 8-10% EtOAc/petroleum ether) to yield 2-bromo-6-chloro-4-(1-cyclobutylethoxy)-3-((trans-4-methylcyclohexyl)methyl)-3H-imidazo[4,5-c]pyridine. MS ES/APCl calc'd. for C20H27BrClN3O [M+H]+ 440. found 440.

Workup

  1. stirringThe reaction was stirred for 30 minutes
  2. customThe reaction was quenched with saturated NH4Cl solution (50 mL) at 0° C.
  3. extractionextracted with EtOAc (2×20 mL)
  4. washThe combined organic extracts were washed with water (20 mL) and brine (20 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography (eluting with 8-10% EtOAc/petroleum ether)

Sources & evidence

ORD record
ord-e3d0fefc049841d2a6c49fb9c9746382
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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