Sodium Carbonate → (S)-4-(3-aminopyrazin-2-yl)-N-(1-(3-chlorophenyl)-2-hydroxyethyl)-2-fluorobenzamide

HRID 595936Notes

Reaction equation

Cl[C:2]1[C:3]([NH2:8])=[N:4][CH:5]=[CH:6][N:7]=1.[Cl:9][C:10]1[CH:11]=[C:12]([C@H:16]([NH:19][C:20]([C:22]2[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][C:23]=2[F:31])=[O:21])[CH2:17][OH:18])[CH:13]=[CH:14][CH:15]=1.C([O-])([O-])=O.[Na+].[Na+].S([O-])([O-])(=O)=O.[Na+].[Na+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.COCCOC>[NH2:8][C:3]1[C:2]([C:25]2[CH:26]=[CH:27][C:22]([C:20]([NH:19][C@@H:16]([C:12]3[CH:13]=[CH:14][CH:15]=[C:10]([Cl:9])[CH:11]=3)[CH2:17][OH:18])=[O:21])=[C:23]([F:31])[CH:24]=2)=[N:7][CH:6]=[CH:5][N:4]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To the reaction mixture of 3-chloropyrazin-2-amine (288 mg, 2.22 mmol), (S)-4-(1-(3-chlorophenyl)-2-hydroxyethylcarbamoyl)-3-fluorophenylboronic acid (500 mg, 1.48 mmol), PdCl2(dppf)-DCM (108 mg, 0.148 mmol), DME (1.1 mL), 2M Na2CO3 (3.703 mL) was added. The reaction mixture was heated at microwave synthesizer (120° C., 12 min). To the reaction mixture, anhydrous sodium sulfate was added, filtered, and concentrated. The crude product was pre-purified by flash chromatography eluting with EtOAc (containing 10% MeOH) in heptane. The pure fractions were combined and concentrated to provide 389 mg of the desired product in 68% yield. LCMS (m/z): 387 (MH+), 0.69 min.

Workup

additionwas added
filtrationfiltered
concentrationconcentrated
customThe crude product was pre-purified by flash chromatography
washeluting with EtOAc (containing 10% MeOH) in heptane
concentrationconcentrated

Sources & evidence

ORD record: ord-32dd453d1ef74f85ab544a75af4fe712
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242996B2

Reaction notes

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