2-Amino-3-chloropyrazine → HCID 57438768, compound

HRID 2233100Notes

Reaction equation

[Cl:1][C:2]1[C:3]([NH2:8])=[N:4][CH:5]=[CH:6][N:7]=1.Br[CH:10]([C:20]1[CH:25]=[CH:24][N:23]=[C:22]([S:26][CH3:27])[N:21]=1)[C:11]([C:13]1[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=1)=O>CN1CCCC1=O.C(Cl)Cl>[Cl:1][C:2]1[C:3]2[N:4]([C:10]([C:20]3[CH:25]=[CH:24][N:23]=[C:22]([S:26][CH3:27])[N:21]=3)=[C:11]([C:13]3[CH:14]=[CH:15][C:16]([F:19])=[CH:17][CH:18]=3)[N:8]=2)[CH:5]=[CH:6][N:7]=1

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of 3-chloropyrazin-2-ylamine (1.3 g, 10 mmol) in 1-methyl-2-pyrrolidinone (1 mL) heated to about 150° C. was added dropwise over about 15 min a solution of 2-bromo-1-(4-fluorophenyl)-2-(2-methylsulfanylpyrimidin-4-yl)ethanone (prepared according to WO2003000682; 0.34 g, 1 mmol) in 1-methyl-2-pyrrolidinone (1 mL). After about 30 min of stirring at about 150° C., the mixture was cooled to ambient temperature, diluted with DCM, extracted three times with 1N HCl and six times with 2N NaOH. The organic layer was dried over Na2SO4 and concentrated. The crude material was purified by silica gel chromatography with heptane/EtOAc (stepwise gradient, 5:1, 3:1) to give 0.019 g (5%) of the title compound: LC/MS (Table 1, Method b) Rt=2.28 min; MS m/z: 372.2 (M+H)+.

Workup

temperaturethe mixture was cooled to ambient temperature
extractionextracted three times with 1N HCl and six times with 2N NaOH
dry with materialThe organic layer was dried over Na2SO4
concentrationconcentrated
customThe crude material was purified by silica gel chromatography with heptane/EtOAc (stepwise gradient, 5:1, 3:1)

Sources & evidence

ORD record: ord-1f38778370114ef6bd9865fb0c95586e
Source dataset: uspto-grants-2010_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07709468B2

Reaction notes

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