2-(Di-tert-butylphosphino)biphenyl → (S)-2-sec-Butylamino-6-(cyclopropanesulfonyl-methylamino)-isonicotinic acid methyl ester

HRID 1436530Notes

Reaction equation

HRID 1436530 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8](Cl)[N:7]=[C:6]([NH:11][C@H:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.[CH3:38][NH:39][S:40]([CH:43]1[CH2:45][CH2:44]1)(=[O:42])=[O:41].[Na]>C1(C)C=CC=CC=1.C1COCC1.C(OCC)(=O)C.C(OCC)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[C:8]([N:39]([S:40]([CH:43]2[CH2:45][CH2:44]2)(=[O:42])=[O:41])[CH3:38])[N:7]=[C:6]([NH:11][C@H:12]([CH2:14][CH3:15])[CH3:13])[CH:5]=1

Participants

9

Reactant 3

HCID 27342152-(Di-tert-butylphosphino)biphenylHCID 68815009Sodium cyclopropanesulfonic acid methylamideHCID 86614996HCID 86614996, compound

Product 1

HCID 68815532(S)-2-sec-Butylamino-6-(cyclopropanesulfonyl-methylamino)-isonicotinic acid methyl ester

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

Dissolve (S)-2-sec-butylamino-6-chloro-isonicotinic acid methyl ester (880 mg, 3.6 mmol), tris(dibenzylideneacetone)dipalladium (0) (164 mg, 0.18 mmol), 2-(di-tert-butylphosphino)biphenyl (107 mg, 0.36 mmol) in toluene (18 mL) and THF (2 mL) in a previously nitrogen-filled sealed vessel. Add sodium cyclopropanesulfonic acid methylamide (700 mg, 4.42 mmol) into the mixture under nitrogen and flush the reactants again with nitrogen before sealing and heating overnight at 100° C. Cool the reaction to room temperature and dilute with ethyl acetate and diethyl ether and filter through a filtering agent. Concentrate and purify (silica gel chromatography, eluting with 0:100 to 08:92 ethyl acetate:hexanes) to give the title compound.

Workup

  1. additionfilled
  2. customsealed vessel
  3. temperatureCool
  4. customthe reaction to room temperature
  5. filtrationfilter through a filtering agent
  6. concentrationConcentrate
  7. custompurify
  8. wash(silica gel chromatography, eluting with 0:100 to 08:92 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-765f9563881148ac8bf7f81f8e5b50c6
Source dataset
uspto-grants-2009_11
Patent number
US07618978B2

Reaction notes

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