1,3-Dibromo-5,5-dimethylhydantoin → HCID 178461228, compound

HRID 1852851Notes

Reaction equation

HRID 1852851 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:26][C@H:27]4[CH2:32][CH2:31][C@H:30]([CH3:33])[CH2:29][CH2:28]4)[C:15]([N:17]4[CH2:22][CH2:21][O:20][C@@H:19]5[CH2:23][CH2:24][CH2:25][C@@H:18]45)=[N:16][C:12]=3[CH:11]=[C:10]([C:34]#[N:35])[N:9]=2)[CH:5]=[N:6][CH:7]=1.[Cl-].[Li+].CC1(C)CCCC(C)(C)N1[Mg]Cl.[Br:50]N1C(C)(C)C(=O)N(Br)C1=O>C1COCC1>[Br:50][C:11]1[C:12]2[N:16]=[C:15]([N:17]3[CH2:22][CH2:21][O:20][C@@H:19]4[CH2:23][CH2:24][CH2:25][C@@H:18]34)[N:14]([CH2:26][C@H:27]3[CH2:32][CH2:31][C@H:30]([CH3:33])[CH2:29][CH2:28]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:34]#[N:35]

Participants

5

Reactant 3

HCID 64791,3-Dibromo-5,5-dimethylhydantoinHCID 178424953HCID 178424953, compoundHCID 178461236HCID 178461236, compound

Product 1

HCID 178461228HCID 178461228, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a −78° C. solution of 4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile (Example 3.2, Step 3; 300 mg, 0.611 mmol) in THF (8 mL) was added 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex (Aldrich, 1M in THF/toluene) (1.22 mL, 1.22 mmol). The resulting yellow solution was stirred at −78° C. for 45 minutes, and then 1,3-dibromo-5,5-dimethylhydantoin (437 mg, 1.527 mmol) was added as a solid in one portion. The reaction was allowed to warm slowly to 0° C. over 90 minutes and then quenched with saturated NH4Cl (10 mL). EtOAc (75 ml) was added, and the organic layer was washed with water and brine (25 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue on a silica gel column eluting with 0 to 50% EtOAc/DCM afforded 7-bromo-4-(5-chloropyridin-3-yl)-2-[(4aR,7aR)-hexahydrocyclopenta[b][1,4]oxazin-4(4aH)-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carbonitrile. MS ESI calc'd for C27H30BrClN6O [M+H]+=571. found=571.

Workup

  1. temperatureto warm slowly to 0° C. over 90 minutes
  2. customquenched with saturated NH4Cl (10 mL)
  3. additionEtOAc (75 ml) was added
  4. washthe organic layer was washed with water and brine (25 mL each)
  5. dry with materialThe organic layer was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification of the residue on a silica gel column
  9. washeluting with 0 to 50% EtOAc/DCM

Sources & evidence

ORD record
ord-c45c9d1cb7e54ad4a426795c7a72eba5
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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