Acetonitrile → 2-amino-5-(3-cyclopropylsulfamoyl-phenyl)-N-methoxy-N-methyl-nicotinamide

HRID 2387216

Reaction equation

HRID 2387216 reaction equation
[NH2:1][C:2]1[N:13]=[CH:12][C:11](Br)=[CH:10][C:3]=1[C:4]([N:6]([O:8][CH3:9])[CH3:7])=[O:5].[CH:15]1([NH:18][S:19]([C:22]2[CH:27]=[CH:26][CH:25]=[C:24](B(O)O)[CH:23]=2)(=[O:21])=[O:20])[CH2:17][CH2:16]1.C(Cl)Cl.CC#N>C([O-])([O-])=O.[Na+].[Na+].COCCOC.O.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]>[NH2:1][C:2]1[N:13]=[CH:12][C:11]([C:24]2[CH:25]=[CH:26][CH:27]=[C:22]([S:19](=[O:20])(=[O:21])[NH:18][CH:15]3[CH2:16][CH2:17]3)[CH:23]=2)=[CH:10][C:3]=1[C:4]([N:6]([O:8][CH3:9])[CH3:7])=[O:5]

Participants

9

Reactant 4

HCID 6342AcetonitrileHCID 6344DichloromethaneHCID 44119335(3-(N-Cyclopropylsulfamoyl)phenyl)boronic acidHCID 596997242-amino-5-bromo-N-methoxy-N-methylnicotinamide

Product 1

HCID 866345442-amino-5-(3-cyclopropylsulfamoyl-phenyl)-N-methoxy-N-methyl-nicotinamide

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Procedure

A suspension of 2-Amino-5-bromo-N-methoxy-N-methyl-nicotinamide (0.2 g, 0.77 mmol), N-cyclopropyl 3-boronobenzenesulfonamide (0.2 g, 0.84 mmol), Pd(dppf)Cl2.DCM (0.063 g, 0.077 mmol) in 2M Na2CO3 (1 ml) and DME (3 ml) is heated at reflux for 1 hour. The crude reaction mixture is subjected to column chromatography (Isolute™ C18, 0-100% MeCN in water −0.1% TFA). All the acetonitrile is removed in vacuo, and the aqueous solution remaining is adjusted to basic pH using NaHCO3. The product is extracted into DCM, and dried (MgSO4). Concentration and drying in vacuo at 40° C. yields the title compound. [M+H]+ 726

Workup

  1. temperatureat reflux for 1 hour
  2. customThe crude reaction mixture
  3. customAll the acetonitrile is removed in vacuo
  4. extractionThe product is extracted into DCM
  5. dry with materialdried (MgSO4)
  6. concentrationConcentration
  7. customdrying in vacuo at 40° C.

Sources & evidence

ORD record
ord-0f769ef43d8646fbb8191300db62f2a9
Source dataset
uspto-grants-2012_09
Patent number
US08268834B2

Linked notes

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