Sodium hydride → (3aRS,6aSR)-1-Methyl-3-(6-phenylethynyl-pyridazin-3-yl)-hexahydro-cyclopentaimidazol-2-one
Reaction equation
[CH3:1][N:2]1[CH:6]2[CH2:7][CH2:8][CH2:9][CH:5]2[NH:4][C:3]1=[O:10].[H-].[Na+].Cl[C:14]1[N:15]=[N:16][C:17]([C:20]#[C:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:18][CH:19]=1>CN(C=O)C>[CH3:1][N:2]1[CH:6]2[CH2:7][CH2:8][CH2:9][CH:5]2[N:4]([C:14]2[N:15]=[N:16][C:17]([C:20]#[C:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)=[CH:18][CH:19]=2)[C:3]1=[O:10]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of (3aRS, 6aSR)-1-methyl-hexahydro-cyclopentaimidazol-2-one (Example 106, step 3) (55 mg, 0.39 mmol, 1.5 equiv.) in 3 ml of DMF was added 60% sodium hydride suspension in mineral oil (17 mg, 0.42 mmol, 1.6 equiv.). The white suspension was stirred for 30 min. at room temperature. Then 3-chloro-6-(phenylethynyl)pyridazine (CAS 77778-15-5) (56 mg, 0.261 mmol) was added and the reaction was stirred for 1 hour at room temperature. After workup with ethyl acetate/water, drying over magnesium sulfate and concentration in vaccuo, the residue was purified by flash chromatography over silica gel eluting with a heptane to 50% ethyl acetate/heptane gradient to yield 40 mg (48% yield) of the title compound as an off-white solid, MS: m/e=319.1 (M+H+).
Workup
- stirringthe reaction was stirred for 1 hour at room temperature
- dry with materialAfter workup with ethyl acetate/water, drying over magnesium sulfate and concentration in vaccuo
- customthe residue was purified by flash chromatography over silica gel eluting with a heptane to 50% ethyl acetate/heptane gradient
Sources & evidence
- ORD record
- ord-6813f9a6aa8146deb7093b9fce963bd7
- Source dataset
- uspto-grants-2016_04
- Patent number
- US09315498B2
Reaction notes
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