Diisopropylethylamine → N-{3-[7-Fluoro-6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]-4-methylphenyl}-3-(2-hydroxy-propan-2-yl)-5-(pentafluoro-lambda6-sulphanyl)benzamide

HRID 1055767Notes

Reaction equation

HRID 1055767 reaction equation
[F:1][C:2]1[C:6]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)=[N:5][N:4]2[CH:13]=[CH:14][N:15]([C:16]3[CH:17]=[C:18]([CH:20]=[CH:21][C:22]=3[CH3:23])[NH2:19])[C:3]=12.[OH:24][C:25]([C:28]1[CH:29]=[C:30]([CH:34]=[C:35]([S:37]([F:42])([F:41])([F:40])([F:39])[F:38])[CH:36]=1)[C:31](O)=[O:32])([CH3:27])[CH3:26].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.C(#N)C>[F:1][C:2]1[C:6]([C:7]2[CH:8]=[N:9][CH:10]=[CH:11][CH:12]=2)=[N:5][N:4]2[CH:13]=[CH:14][N:15]([C:16]3[CH:17]=[C:18]([NH:19][C:31](=[O:32])[C:30]4[CH:34]=[C:35]([S:37]([F:42])([F:38])([F:39])([F:40])[F:41])[CH:36]=[C:28]([C:25]([OH:24])([CH3:27])[CH3:26])[CH:29]=4)[CH:20]=[CH:21][C:22]=3[CH3:23])[C:3]=12

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 86690975HCID 86690975, compoundHCID 896997403-[7-Fluoro-6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]-4-methylaniline

Product 1

HCID 89699870N-{3-[7-Fluoro-6-(pyridin-3-yl)-1H-imidazo[1,2-b]pyrazol-1-yl]-4-methylphenyl}-3-(2-hydroxy-propan-2-yl)-5-(pentafluoro-lambda6-sulphanyl)benzamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Procedure

60 mg (0.195 mmol) of the compound of Example 83A and 60 mg (0.195 mmol) of the compound of Example 19A were dissolved in 2 ml of DMF, and 89 mg (0.234 mmol) of HATU and 41 μl (0.234 mmol) of N,N-diisopropylethylamine were added in succession. After about 16 h of stirring at RT, the reaction mixture was diluted with 1 ml of acetonitrile and separated into its components by preparative HPLC (Method 36). The product fractions were combined and freed from the solvent on a rotary evaporator. The residue was dissolved in a little methanol and the solution was passed through a bicarbonate cartridge (from Polymerlabs, Stratospheres SPE, PL-HCO3 MP SPE, capacity 0.9 mmol) to convert the formate salt obtained after preparative HPLC into the free base. Evaporation and drying under high vacuum gave 42 mg (35% of theory) of the title compound.

Workup

  1. customseparated into its components by preparative HPLC (Method 36)
  2. customfreed from the solvent on a rotary evaporator
  3. dissolutionThe residue was dissolved in a little methanol
  4. customobtained after preparative HPLC into the free base
  5. customEvaporation
  6. customdrying under high vacuum

Sources & evidence

ORD record
ord-356fd778916044ee8861e0cad7115f88
Source dataset
uspto-grants-2016_07
Patent number
US09394309B2

Reaction notes

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