Hydrochloric Acid → HCID 178457299, compound

HRID 2274439Notes

Reaction equation

HRID 2274439 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:15]=[C:14]([C:16]4[C:20]([NH:21][C:22](=[O:30])[N:23]([CH2:27][CH2:28][CH3:29])[CH2:24][CH2:25][CH3:26])=[CH:19][N:18](C5CCCCO5)[N:17]=4)[NH:13][C:12]=3[CH:37]=2)[CH2:4][CH2:3]1.Cl>O1CCOCC1.[OH-].[Na+]>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:9]=[CH:10][C:11]3[N:15]=[C:14]([C:16]4[C:20]([NH:21][C:22](=[O:30])[N:23]([CH2:27][CH2:28][CH3:29])[CH2:24][CH2:25][CH3:26])=[CH:19][NH:18][N:17]=4)[NH:13][C:12]=3[CH:37]=2)[CH2:4][CH2:3]1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 136363655HCID 136363655, compound

Product 1

HCID 178457299HCID 178457299, compoundYield 41%

Reagents, catalysts & solvents 2

HCID 14798Sodium HydroxideSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 190 mg of 3-[3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]-1,1-dipropylurea in solution in 3.5 mL of a 4N solution of hydrochloric acid in dioxane is stirred at 22° C. for 4 hours. A solid precipitates. The solid is filtered off and washed with dioxane and with isopropyl ether. The solid becomes pasty. Filtrate and precipitate are grouped together with methanol and the mixture is concentrated. The reaction crude is dissolved in a 2N aqueous solution of NaOH, and a sticky paste forms, which does not dissolve. It is recovered with methanol and the product is concentrated. The concentrate is dissolved in 10 mL of water and extracted with 2 times 10 mL and 2 times 15 mL of ethyl acetate. The organic phases are dried over MgSO4, filtered and concentrated under vacuum in a rotary evaporator. The precipitate obtained is purified by preparative HPLC with, as eluent, a gradient of water/acetonitrile containing respectively 0.07% of trifluoroacetic acid. 65 mg of 3-{3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyrazol-4-yl}-1,1-dipropylurea are obtained in the form of a yellow solid. 1H NMR (400 MHz, DMSO-d6, δ in ppm): 0.89 (t, J=7.5 Hz, 6H); 1.57 (m, 4H); 2.89 (s, 3H); 3.03 (m, 2H); 3.23 (m partially masked, 2H); 3.29 (m, 4H); 3.57 (m, 2H); 3.87 (m, 2H); 7.13 (d, J=2.0 Hz, 1H); 7.24 (broad d, J=9.0 Hz, 1H); 7.59 (d, J=9.0 Hz, 1H); 7.98 (s, 1H).

Workup

  1. customA solid precipitates
  2. filtrationThe solid is filtered off
  3. washwashed with dioxane and with isopropyl ether
  4. concentrationthe mixture is concentrated
  5. customThe reaction crude
  6. dissolutiona sticky paste forms, which does not dissolve
  7. customIt is recovered with methanol
  8. concentrationthe product is concentrated
  9. dissolutionThe concentrate is dissolved in 10 mL of water
  10. extractionextracted with 2 times 10 mL and 2 times 15 mL of ethyl acetate
  11. dry with materialThe organic phases are dried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated under vacuum in a rotary evaporator
  14. customThe precipitate obtained
  15. customis purified by preparative HPLC with, as eluent

Sources & evidence

ORD record
ord-5d0307feb53b497c80a385f37b04c65b
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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