Chloroform → (R)-2-(2-benzyl-1H-imidazol-1-yl)-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one

HRID 44844Notes

Reaction equation

HRID 44844 reaction equation
Br[C:2]1[N:3]([C:7]2[N:16]=[CH:15][C:14]3[N:13]([CH3:17])[C:12](=[O:18])[C@@H:11]([CH2:19][CH3:20])[N:10]([CH:21]4[CH2:25][CH2:24][CH2:23][CH2:22]4)[C:9]=3[N:8]=2)[CH:4]=[CH:5][N:6]=1.C(Cl)(Cl)Cl.[C:30]1([C:45]2C=CC=CC=2)[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1P(C(C)(C)C)C(C)(C)C.[Br-].C([Zn+])C1C=CC=CC=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:45]([C:2]1[N:3]([C:7]2[N:16]=[CH:15][C:14]3[N:13]([CH3:17])[C:12](=[O:18])[C@@H:11]([CH2:19][CH3:20])[N:10]([CH:21]4[CH2:25][CH2:24][CH2:23][CH2:22]4)[C:9]=3[N:8]=2)[CH:4]=[CH:5][N:6]=1)[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1

Participants

6

Reactant 4

HCID 6212ChloroformHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 58405307(R)-2-(2-bromo-1H-imidazol-1-yl)-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-oneHCID 178419772HCID 178419772, compound

Product 1

HCID 58405913(R)-2-(2-benzyl-1H-imidazol-1-yl)-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-oneYield 293.7%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
90 °C

Procedure

(R)-2-(2-bromo-1H-imidazol-1-yl)-8-cyclopentyl-7-ethyl-5-methyl-7,8-dihydropteridin-6(5H)-one (Example 65, 0.21 g, 0.518 mmol), Pd2(dba)3, CHCl3 (53 mg, 0.0518 mmol) and biphenyl-2-yldi-tert-butylphosphine (30 mg, 0.103 mmol) were placed in a screw cap vial and a solution of benzyl zinc bromide (1.5 mL, 0.777 mmol in THF) was added. A stream of nitrogen was bubbled through the mixture for 2 minutes and then the vial was sealed and the resulting solution was stirred at 90° C. for 18 h. The reaction mixture was filtered, then purified by flash chromatography with a silica gel column by eluting with a mixture of Hexane:EtOAc and then further purified by preparative HPLC to give the title compound (126 mg). LCMS: 417.2 m/z (M+H)+; ret. Time: 3.80 min (Analytical Method A).

Workup

  1. customcap vial
  2. customA stream of nitrogen was bubbled through the mixture for 2 minutes
  3. customthe vial was sealed
  4. filtrationThe reaction mixture was filtered
  5. custompurified by flash chromatography with a silica gel column
  6. washby eluting with a mixture of Hexane
  7. customEtOAc and then further purified by preparative HPLC

Sources & evidence

ORD record
ord-20b325c96e28429a890d4ab729ab2f4b
Source dataset
uspto-grants-2013_09
Patent number
US08541418B2

Reaction notes

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