1,3-Dibromo-5,5-dimethylhydantoin → HCID 178461214, compound

HRID 1852846Notes

Reaction equation

HRID 1852846 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:29][C@H:30]4[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]4)[C:15]([N:17]4[CH2:22][CH2:21][O:20][CH2:19][C@H:18]4[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)=[N:16][C:12]=3[CH:11]=[C:10]([C:37]#[N:38])[N:9]=2)[CH:5]=[N:6][CH:7]=1.[Cl-].[Cl-].CC1(C)CCCC(C)(C)[N-]1.[Mg+2].[Li+].[Br:53]N1C(C)(C)C(=O)N(Br)C1=O>C1COCC1>[Br:53][C:11]1[C:12]2[N:16]=[C:15]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][C@H:18]3[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[N:14]([CH2:29][C@H:30]3[CH2:35][CH2:34][C@H:33]([CH3:36])[CH2:32][CH2:31]3)[C:13]=2[C:8]([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)=[N:9][C:10]=1[C:37]#[N:38]

Participants

5

Reactant 3

HCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 25150783Lithium magnesium 2,2,6,6-tetramethylpiperidin-1-ide dichlorideHCID 178461221HCID 178461221, compound

Product 1

HCID 178461214HCID 178461214, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

4-(5-Chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Example 2.1, Step 4; 180 mg, 0.342 mmol) was taken up in THF (3415 μl) and cooled to −78° C. Lithium magnesium 2,2,6,6-tetramethylpiperidin-1-ide dichloride (1 M solution in THF/toluene, 683 μl, 0.683 mmol) was added, and the mixture was stirred at −78° C. for 45 minutes. 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione (244 mg, 0.854 mmol) was then added. The cooling bath was removed, and the solution warmed to room temperature and stirred for 60 minutes. The mixture was then diluted with ethyl acetate and washed with sodium thiosulfate (2×) and brine (1×). The organic layer was dried over magnesium sulfate, filtered, and concentrated. The resulting residue was purified via silica gel chromatography (0-100% ethyl acetate/hexanes) to afford 7-bromo-4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-[(3R)-3-phenylmorpholin-4-yl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile as a white solid that was contaminated with unreacted starting material. MS ESI calc'd. for C30H30BrClN6O [M+1]+, [M+3]+605, 607. found 605, 607.

Workup

  1. customThe cooling bath was removed
  2. temperaturethe solution warmed to room temperature
  3. stirringstirred for 60 minutes
  4. additionThe mixture was then diluted with ethyl acetate
  5. washwashed with sodium thiosulfate (2×) and brine (1×)
  6. dry with materialThe organic layer was dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified via silica gel chromatography (0-100% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-d5d5534c51a54b9a88e6909e9e640c09
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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