Diisopropylethylamine → 7-formyl-1-methyl-1H-indole-2-carboxylic acid (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl)-amide

HRID 2360481Notes

Reaction equation

HRID 2360481 reaction equation
[CH:1]([C:3]1[CH:4]=[CH:5][CH:6]=[C:7]2[C:11]=1[N:10]([CH3:12])[C:9]([C:13]([OH:15])=O)=[CH:8]2)=[O:2].N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.ON1C2N=CC=CC=2N=N1.Cl.[NH2:60][C:61]1[C:62]([O:76][CH3:77])=[C:63]([NH:71][S:72]([CH3:75])(=[O:74])=[O:73])[CH:64]=[C:65]([C:67]([CH3:70])([CH3:69])[CH3:68])[CH:66]=1>CN(C)C=O.C(OCC)(=O)C.O>[C:67]([C:65]1[CH:64]=[C:63]([NH:71][S:72]([CH3:75])(=[O:74])=[O:73])[C:62]([O:76][CH3:77])=[C:61]([NH:60][C:13]([C:9]2[N:10]([CH3:12])[C:11]3[C:7]([CH:8]=2)=[CH:6][CH:5]=[CH:4][C:3]=3[CH:1]=[O:2])=[O:15])[CH:66]=1)([CH3:70])([CH3:68])[CH3:69]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 21079205N-(3-amino-5-tert-butyl-2-methoxyphenyl)methanesulphonamide-hydrochlorideHCID 58493932HCID 58493932, compound

Product 1

HCID 598566117-formyl-1-methyl-1H-indole-2-carboxylic acid (5-tert-butyl-3-methanesulfonylamino-2-methoxy-phenyl)-amide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

1.45 g 7-formyl-1-methyl-1H-indole-2-carboxylic acid (salt with N-methyl-morpholine) are dissolved in 8 ml N,N-dimethylformamide and combined with 2.72 g O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium-hexafluorophosphate (HATU), 2.45 ml N,N-diisopropyl-ethylamine (DIEA) as well as 324 mg 1-hydroxy-7-azabenzotriazole (HOAT). The mixture is left for 15 minutes at ambient temperature with stirring and then 1.47 g N-(3-amino-5-tert-butyl-2-methoxy-phenyl)-methanesulphonamide hydrochloride are added. The reaction is heated to 50° C. for 12 hours and then divided between water and ethyl acetate. The organic phase is washed successively with 1 N hydrochloric acid, water and saturated aqueous sodium chloride solution and dried on magnesium sulphate. After elimination of the solvents in vacuo the residue is chromatographed on silica gel with cyclohexane/ethyl acetate (70:30 to 20:80).

Workup

  1. washThe organic phase is washed successively with 1 N hydrochloric acid, water and saturated aqueous sodium chloride solution
  2. customdried on magnesium sulphate
  3. customAfter elimination of the solvents in vacuo the residue is chromatographed on silica gel with cyclohexane/ethyl acetate (70:30 to 20:80)

Sources & evidence

ORD record
ord-2f08c3b5baed4f88b8ef3ba173958d76
Source dataset
uspto-grants-2014_04
Patent number
US08686022B2

Reaction notes

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