Hydrochloric Acid → HCID 178457928, compound

HRID 2274438Notes

Reaction equation

HRID 2274438 reaction equation
[CH:1]([N:4]([CH:35]([CH3:37])[CH3:36])[C:5]([NH:7][C:8]1[C:9]([C:19]2[NH:23][C:22]3[CH:24]=[C:25]([N:28]4[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]4)[CH:26]=[CH:27][C:21]=3[N:20]=2)=[N:10][N:11](C2CCCCO2)[CH:12]=1)=[O:6])([CH3:3])[CH3:2].Cl>O1CCOCC1>[CH:35]([N:4]([CH:1]([CH3:3])[CH3:2])[C:5]([NH:7][C:8]1[C:9]([C:19]2[NH:23][C:22]3[CH:24]=[C:25]([N:28]4[CH2:33][CH2:32][N:31]([CH3:34])[CH2:30][CH2:29]4)[CH:26]=[CH:27][C:21]=3[N:20]=2)=[N:10][NH:11][CH:12]=1)=[O:6])([CH3:37])[CH3:36]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 136388009HCID 136388009, compound

Product 1

HCID 178457928HCID 178457928, compoundYield 51.6%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of 230 mg of 1,1-diisopropyl-3-[3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]urea in solution in 40 eq of a 4N solution of hydrochloric acid in dioxane is stirred at 22° C. for approximately 4 hours, and precipitation occurs. The suspension is filtered through sintered glass and the solid is rinsed with dioxane and with isopropyl ether. The precipitate is dried in an oven. The precipitate is dissolved in 5 mL of 2N NaOH, and then extracted with 2 times 5 mL of ethyl acetate then 2 times 10 mL of ethyl acetate. The organic phases are dried over MgSO4, filtered and concentrated under vacuum in a rotary evaporator. The concentrate is purified by preparative HPLC with, as eluent, a gradient of water/acetonitrile containing respectively 0.07% of trifluoroacetic acid. 99 mg of 1,1-diisopropyl-3-{3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl}urea are isolated in the form of a pale yellow powder. 1H NMR (400 MHz, DMSO-d6, δ in ppm): 1.25 (d, J=7.0 Hz, 12H); 2.90 (s, 3H); 3.03 (m, 2H); 3.23 (m, 2H); 3.58 (m, 2H); 3.87 (m, 4H); 7.12 (d, J=2.0 Hz, 1H); 7.24 (dd, J=2.0 and 9.0 Hz, 1H); 7.58 (d, J=9.0 Hz, 1H); 7.98 (s, 1H).

Workup

  1. customprecipitation
  2. filtrationThe suspension is filtered through sintered glass
  3. washthe solid is rinsed with dioxane and with isopropyl ether
  4. customThe precipitate is dried in an oven
  5. dissolutionThe precipitate is dissolved in 5 mL of 2N NaOH
  6. extractionextracted with 2 times 5 mL of ethyl acetate
  7. dry with materialThe organic phases are dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under vacuum in a rotary evaporator
  10. customThe concentrate is purified by preparative HPLC with, as eluent

Sources & evidence

ORD record
ord-c83a50d7de4745cebad15e6965f554db
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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