Ammonia → 6-(4'-(2-Amino-2-oxoethyl)-2'-chlorobiphenyl-4-yl)-3,5-dimethylpyrazine-2-carboxamide
Reaction equation
[C:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]3[CH:21]=[CH:20][C:19]([CH2:22][C:23](OC)=[O:24])=[CH:18][C:17]=3[Cl:27])=[CH:12][CH:11]=2)[C:7]([CH3:28])=[N:6][C:5]=1[CH3:29])(=[O:3])[NH2:2].[NH3:30]>>[NH2:30][C:23](=[O:24])[CH2:22][C:19]1[CH:20]=[CH:21][C:16]([C:13]2[CH:14]=[CH:15][C:10]([C:8]3[N:9]=[C:4]([C:1]([NH2:2])=[O:3])[C:5]([CH3:29])=[N:6][C:7]=3[CH3:28])=[CH:11][CH:12]=2)=[C:17]([Cl:27])[CH:18]=1Participants
Conditions
- Temperature
- 140 °C
Procedure
Methyl 2-(4′-(6-carbamoyl-3,5-dimethylpyrazin-2-yl)-2-chlorobiphenyl-4-yl)acetate (Intermediate 1-1; 60 mg, 0.15 mmol) and ammonia (7M in methanol) (2091 μL, 14.64 mmol) were sealed into a microwave tube. The reaction was heated to 140° C. for 1 hour in the microwave reactor and cooled to RT. Removal of the solvent under reduced pressure gave crude product. The crude product was purified by preparative HPLC (Waters—Xbridge Prep C18 5 μm), using decreasingly polar mixtures of water (containing 0.1% formic acid) and {MeOH(3):MeCN(1)} as eluents. Fractions containing the desired compound were evaporated to dryness to afford 6-(4′-(2-amino-2-oxoethyl)-2′-chlorobiphenyl-4-yl)-3,5-dimethylpyrazine-2-carboxamide (16.20 mg, 28.0%) as a colourless solid.
Workup
- temperaturecooled to RT
- customRemoval of the solvent under reduced pressure
- customgave crude product
- customThe crude product was purified by preparative HPLC (Waters—Xbridge Prep C18 5 μm)
- additionFractions containing the desired compound
- customwere evaporated to dryness
Sources & evidence
- ORD record
- ord-a8fb1d4eec8b422cb98909dc22b42180
- Source dataset
- uspto-grants-2012_05
- Patent number
- US08188092B2
Reaction notes
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