Hydrochloric Acid → HCID 178522438, compound

HRID 2274384Notes

Reaction equation

HRID 2274384 reaction equation
[F:1][C:2]1[C:30]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)=[CH:29][C:5]2[NH:6][C:7]([C:9]3[C:13]([NH:14][C:15]([N:17]4[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]4)=[O:16])=[CH:12][N:11](C4CCCCO4)[N:10]=3)=[N:8][C:4]=2[CH:3]=1.Cl>O1CCOCC1.CO>[F:1][C:2]1[C:30]([N:31]2[CH2:36][CH2:35][O:34][CH2:33][CH2:32]2)=[CH:29][C:5]2[NH:6][C:7]([C:9]3[C:13]([NH:14][C:15]([N:17]4[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]4)=[O:16])=[CH:12][NH:11][N:10]=3)=[N:8][C:4]=2[CH:3]=1

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 178522371HCID 178522371, compound

Product 1

HCID 178522438HCID 178522438, compoundYield 96.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 4 g of piperidine-1-carboxylic acid [3-(5-fluoro-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]amide in solution in 50 mL of a 4N solution of hydrochloric acid in dioxane is stirred at 22° C. for 4 hours. In order for the reaction to be complete, the reaction medium is concentrated and again dissolved in 50 mL of a 4N solution of hydrochloric acid in dioxane and left stirring at ambient temperature for 18 hours. The suspension is filtered over sintered glass and the solid is washed with dioxane. After spin-filter-drying, the solid is triturated in isopropyl ether. Since the solid obtained is hygroscopic, it is taken up in methanol and the solution is concentrated under vacuum. The oil obtained is purified by flash chromatography on an Intelliflash apparatus on an analogix RS-120 cartridge. The elution is carried out with dichloromethane then ethyl acetate at 100%, and then with a 95/5 mixture of dichloromethane/methanol. After concentration of the fractions containing the product, the latter is triturated in isopropyl ether and the solid obtained is filtered and dried under vacuum until the weight is constant. 3.2 g of piperidine-1-carboxylic acid [3-(5-fluoro-6-morpholin-4-yl-1H-benzimidazol-2-yl)-1H-pyrazol-4-yl]amide are obtained in hydrochloride form. 1H NMR (300 MHz, (CD3)2SO, δ in ppm): 1.48-1.67 (m: 6H); 3.03 (m: 4H); 3.48 (m: 4H); 3.78 (m: 4H); 7.18 (d, J=8 Hz: 1H); 7.46 (d, J=12 Hz: 1H); 8.01 (s: 1H); 9.53 (broad s: 1H); 12.50 (very broad s: 1H).

Workup

  1. customIn order for the reaction
  2. concentrationthe reaction medium is concentrated
  3. dissolutionagain dissolved in 50 mL of a 4N solution of hydrochloric acid in dioxane
  4. waitleft
  5. filtrationThe suspension is filtered over sintered glass
  6. washthe solid is washed with dioxane
  7. customAfter spin-filter-drying
  8. customthe solid is triturated in isopropyl ether
  9. customSince the solid obtained
  10. concentrationthe solution is concentrated under vacuum
  11. customThe oil obtained
  12. customis purified by flash chromatography on an Intelliflash apparatus on an analogix RS-120 cartridge
  13. washThe elution
  14. additionethyl acetate at 100%, and then with a 95/5 mixture of dichloromethane/methanol
  15. additionAfter concentration of the fractions containing the product
  16. customthe latter is triturated in isopropyl ether
  17. customthe solid obtained
  18. filtrationis filtered
  19. customdried under vacuum until the weight

Sources & evidence

ORD record
ord-fbad5c8525924302abb0ac541a743512
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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