Diisopropylethylamine → 3-Cyano-N-{2-methyl-3-[6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-5-(pentafluoro-lambda6-sulphanyl)benzamide

HRID 1055743Notes

Reaction equation

HRID 1055743 reaction equation
[CH3:1][C:2]1[C:8]([N:9]2[C:16]3[N:12]([N:13]=[C:14]([C:17]4[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=4)[CH:15]=3)[CH:11]=[CH:10]2)=[CH:7][CH:6]=[CH:5][C:3]=1[NH2:4].[C:23]([C:25]1[CH:26]=[C:27]([CH:31]=[C:32]([S:34]([F:39])([F:38])([F:37])([F:36])[F:35])[CH:33]=1)[C:28](O)=[O:29])#[N:24].CN(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>CN(C=O)C.O>[C:23]([C:25]1[CH:26]=[C:27]([CH:31]=[C:32]([S:34]([F:38])([F:39])([F:35])([F:36])[F:37])[CH:33]=1)[C:28]([NH:4][C:3]1[CH:5]=[CH:6][CH:7]=[C:8]([N:9]2[C:16]3[N:12]([N:13]=[C:14]([C:17]4[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=4)[CH:15]=3)[CH:11]=[CH:10]2)[C:2]=1[CH3:1])=[O:29])#[N:24]

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 896997682-Methyl-3-[6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]anilineHCID 896998123-Cyano-5-(pentafluoro-lambda6-sulphanyl)benzoic acid

Product 1

HCID 897002763-Cyano-N-{2-methyl-3-[6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]phenyl}-5-(pentafluoro-lambda6-sulphanyl)benzamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

100 mg (0.346 mmol) of the compound of Example 69A and 111 mg (0.346 mmol, 85% pure) of the compound from Example 23A were dissolved in 1.9 ml of anhydrous DMF and 158 mg (0.415 mmol) of HATU and 72 μl (0.415 mmol) of N,N-diisopropylethylamine were added in succession. The reaction mixture was stirred at RT overnight (about 15 h) and then stirred into about 10 ml of water. The resulting precipitate was filtered off with suction, dissolved in dichloromethane and washed successively with semisaturated aqueous sodium bicarbonate solution and saturated sodium chloride solution. After drying over anhydrous magnesium sulphate, filtration and removal of the solvent on a rotary evaporator, the residue obtained in this manner was purified by preparative HPLC (Method 33). After evaporation of the product fractions, the solid was re-dissolved in ethyl acetate and washed with saturated aqueous sodium bicarbonate solution to convert the product into the form of the free base. After drying of the organic phase over anhydrous magnesium sulphate, filtration and evaporation, the product was finally triturated with 3 ml of pentane to which a few drops of diisopropyl ether had been added. Filtration with suction and drying of the solid under high vacuum gave 66 mg (35% of theory) of the title compound.

Workup

  1. filtrationThe resulting precipitate was filtered off with suction
  2. dissolutiondissolved in dichloromethane
  3. washwashed successively with semisaturated aqueous sodium bicarbonate solution and saturated sodium chloride solution
  4. dry with materialAfter drying over anhydrous magnesium sulphate, filtration and removal of the solvent on a rotary evaporator
  5. customthe residue obtained in this manner
  6. customwas purified by preparative HPLC (Method 33)
  7. customAfter evaporation of the product fractions
  8. dissolutionthe solid was re-dissolved in ethyl acetate
  9. washwashed with saturated aqueous sodium bicarbonate solution
  10. dry with materialAfter drying of the organic phase over anhydrous magnesium sulphate, filtration and evaporation
  11. customthe product was finally triturated with 3 ml of pentane to which a few drops of diisopropyl ether
  12. additionhad been added
  13. filtrationFiltration with suction
  14. customdrying of the solid under high vacuum

Sources & evidence

ORD record
ord-7c5a260af8474a8eb828165c4141c1d9
Source dataset
uspto-grants-2016_07
Patent number
US09394309B2

Reaction notes

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