Diisopropylethylamine → N-{2,4-Dimethyl-5-[6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-3-formyl-5-(penta-fluoro-lambda6-sulphanyl)benzamide

HRID 1055689Notes

Reaction equation

HRID 1055689 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([S:12]([F:17])([F:16])([F:15])([F:14])[F:13])[CH:11]=1)[C:6](O)=[O:7])=[O:2].[CH3:18]N(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.C[C:52]1[C:58]([N:59]2[C:66]3[N:62]([N:63]=[C:64]([C:67]4[CH:68]=[N:69][CH:70]=[CH:71][CH:72]=4)[CH:65]=3)[CH:61]=[CH:60]2)=[C:57]([CH3:73])[CH:56]=[CH:55][C:53]=1[NH2:54]>CN(C=O)C.O>[CH3:18][C:55]1[CH:56]=[C:57]([CH3:73])[C:58]([N:59]2[C:66]3[N:62]([N:63]=[C:64]([C:67]4[CH:68]=[N:69][CH:70]=[CH:71][CH:72]=4)[CH:65]=3)[CH:61]=[CH:60]2)=[CH:52][C:53]=1[NH:54][C:6](=[O:7])[C:5]1[CH:9]=[C:10]([S:12]([F:17])([F:16])([F:15])([F:14])[F:13])[CH:11]=[C:3]([CH:1]=[O:2])[CH:4]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 89699939HCID 89699939, compoundHCID 896999913-Formyl-5-(pentafluoro-lambda6-sulphanyl)benzoic acid

Product 1

HCID 86690986N-{2,4-Dimethyl-5-[6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-3-formyl-5-(penta-fluoro-lambda6-sulphanyl)benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

214 mg (0.659 mmol, 85% pure) of the compound from Example 36A and 301 mg (0.791 mmol) of HATU were dissolved in 2.3 ml of anhydrous DMF, and 140 μl (0.791 mmol) of N,N-diisopropylethylamine were added. After 30 min, 200 mg (0.659 mmol) of the compound of Example 11A were added. After the reaction mixture had been stirred at RT for 1.5 h, about 50 ml of water were added and the mixture was extracted three times with in each case about 50 ml of ethyl acetate. The combined organic extracts were washed with saturated sodium chloride solution, dried over anhydrous magnesium sulphate, filtered and freed from the solvent on a rotary evaporator. The crude product obtained in this manner was purified by MPLC (30 g of silica gel, mobile phase gradient cyclohexane/ethyl acetate 1:1→1:5). Evaporation of the product fractions and drying of the residue under high vacuum gave 160 mg (36% of theory, 85% pure) of the title compound.

Workup

  1. extractionthe mixture was extracted three times with in each case about 50 ml of ethyl acetate
  2. washThe combined organic extracts were washed with saturated sodium chloride solution
  3. dry with materialdried over anhydrous magnesium sulphate
  4. filtrationfiltered
  5. customfreed from the solvent on a rotary evaporator
  6. customThe crude product obtained in this manner
  7. customwas purified by MPLC (30 g of silica gel, mobile phase gradient cyclohexane/ethyl acetate 1:1→1:5)
  8. customEvaporation of the product fractions
  9. customdrying of the residue under high vacuum

Sources & evidence

ORD record
ord-960ebd8e1d3d47cf932f444b7ac05781
Source dataset
uspto-grants-2016_07
Patent number
US09394309B2

Reaction notes

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