Cesium carbonate → 2-Cyclopropylamino-6-(methanesulfonyl-methylamino)-isonicotinic acid methylester

HRID 732442Notes

Reaction equation

C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:53][O:54][C:55](=[O:69])[C:56]1[CH:61]=[C:60]([N:62]([S:64]([CH3:67])(=[O:66])=[O:65])[CH3:63])[N:59]=[C:58](Cl)[CH:57]=1.[CH:70]1([NH2:73])[CH2:72][CH2:71]1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH3:53][O:54][C:55](=[O:69])[C:56]1[CH:61]=[C:60]([N:62]([S:64]([CH3:67])(=[O:66])=[O:65])[CH3:63])[N:59]=[C:58]([NH:73][CH:70]2[CH2:72][CH2:71]2)[CH:57]=1

Participants

Conditions

Temperature: 90 °C

Procedure

Add palladium acetate (29 mg, 0.13 mmol), racemic 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (81 mg, 0.13 mmol), cesium carbonate (531 mg, 1.63 mmol), toluene (10 mL), and 2-chloro-6-(methanesulfonyl-methylamino)-isonicotinic acid methyl ester (347 mg, 1.25 mmol) to a sealed tube. After degassing the reaction vessel with nitrogen, add cyclopropylamine (0.114 mL, 1.63 mmol) to the reaction mixture. Heat the reaction vessel at 90° C. overnight. Cool to room temperature and filter the solids through a filtering agent. Wash with ethyl acetate. Concentrate the combined filtrates and purify (silica gel chromatography, eluting with 30:70 ethyl acetate:hexanes) to give the title compound (261 mg 70%).

Workup

customAfter degassing the reaction vessel with nitrogen
temperatureCool to room temperature
filtrationfilter the solids through a filtering agent
washWash with ethyl acetate
concentrationConcentrate the combined filtrates
custompurify
wash(silica gel chromatography, eluting with 30:70 ethyl acetate:hexanes)

Sources & evidence

ORD record: ord-a6ce1e0a537c46eaaf4311f049ba510d
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07585885B2

Reaction notes

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