Hydrochloric Acid → HCID 178464318, compound

HRID 2274398Notes

Reaction equation

HRID 2274398 reaction equation
[CH2:1]([N:3]([CH2:38][CH3:39])[C:4]([NH:6][C:7]1[C:8]([C:18]2[NH:22][C:21]3[CH:23]=[C:24]([O:28][CH2:29][CH2:30][CH2:31][N:32]4[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]4)[C:25]([F:27])=[CH:26][C:20]=3[N:19]=2)=[N:9][N:10](C2CCCCO2)[CH:11]=1)=[O:5])[CH3:2].[ClH:40]>O1CCOCC1>[ClH:40].[CH2:38]([N:3]([CH2:1][CH3:2])[C:4]([NH:6][C:7]1[C:8]([C:18]2[NH:22][C:21]3[CH:23]=[C:24]([O:28][CH2:29][CH2:30][CH2:31][N:32]4[CH2:37][CH2:36][CH2:35][CH2:34][CH2:33]4)[C:25]([F:27])=[CH:26][C:20]=3[N:19]=2)=[N:9][NH:10][CH:11]=1)=[O:5])[CH3:39]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 178464307HCID 178464307, compound

Product 1

HCID 178464318HCID 178464318, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

70 mg of 1,1-diethyl-3-[3-[5-fluoro-6-(3-piperidin-1-ylpropoxy)-1H-benzimidazol-2-yl]-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]urea are suspended in 3 mL of a 3N solution of HCl in dioxane. The medium is stirred at ambient temperature for 48 hours. The solvent is evaporated off under vacuum in a rotary evaporator. The reaction crude is purified by flash chromatography on a 4 g silica cartridge, eluent: 100/0 to 80/20 dichloromethane/methanol. The fractions containing the expected product are concentrated and the solid obtained is triturated in isopropyl ether. After filtration and rinsing of the solid, 26.2 mg of 1,1-diethyl-3-{3-[5-fluoro-6-(3-piperidin-1-ylpropoxy)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl}urea hydrochloride are isolated in the form of a sand-colored solid. 1H NMR (400 MHz, DMSO-d6, δ in ppm) after addition of a drop of TFA-d1 (CF3COOD-d1): 1.15 (t, J=7.0 Hz, 6H); 1.39 (m, 1H); from 1.57 to 1.76 (m, 3H); 1.83 (m, 2H); 2.22 (m, 2H); 2.93 (m, 2H); 3.25 (m, 2H); 3.37 (q, J=7.0 Hz, 4H); 3.51 (m, 2H); 4.21 (t, J=6.0 Hz, 2H); 7.34 (d, J=7.5 Hz, 1H); 7.56 (d, J=11.0 Hz, 1H); 8.00 (s, 1H).

Workup

  1. customThe solvent is evaporated off under vacuum in a rotary evaporator
  2. customThe reaction crude
  3. customis purified by flash chromatography on a 4 g silica cartridge, eluent
  4. additionThe fractions containing the expected product
  5. concentrationare concentrated
  6. customthe solid obtained
  7. customis triturated in isopropyl ether
  8. filtrationAfter filtration
  9. washrinsing of the solid, 26.2 mg of 1,1-diethyl-3-{3-[5-fluoro-6-(3-piperidin-1-ylpropoxy)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl}urea hydrochloride
  10. customare isolated in the form of a sand-colored solid
  11. addition1H NMR (400 MHz, DMSO-d6, δ in ppm) after addition of a drop of TFA-d1 (CF3COOD-d1)

Sources & evidence

ORD record
ord-c48981fd01884731afa4ab7741706d5d
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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