Hydrochloric Acid → HCID 178522436, compound

HRID 2274440Notes

Reaction equation

HRID 2274440 reaction equation
[F:1][C:2]1[C:30]([N:31]2[CH2:37][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>[F:1][C:2]1[C:30]([N:31]2[CH2:37][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

4

Reactant 2

HCID 313Hydrochloric AcidHCID 178522370HCID 178522370, compound

Product 1

HCID 178522436HCID 178522436, compoundYield 97.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
22 °C

Procedure

A solution of 80 mg of N-[3-(5-fluoro-6-perhydro-1,4-oxazepin-4-yl-1H-benzimidazol-2-yl)-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]piperidine-1-carboxamide in solution in 4 mL of a 4N solution of hydrochloric acid in dioxane is stirred at 22° C. for 1 hour. The reaction medium is concentrated under vacuum in a rotary evaporator, and then reacted again at 22° C. for 16 hours with 4 mL of a 4N solution of hydrochloric acid in dioxane is stirred at 22° C. The reaction medium is concentrated under vacuum in a rotary evaporator. The product is made into a paste in isopropyl ether, but the product is hydroscopic. The reaction crude is purified by flash chromatography, elution being carried out with a mixture of cyclohexane/ethyl acetate then dichloromethane/methanol. The product is diluted in ethyl acetate, and washed with 2 times 5 mL of a 2N aqueous solution of sodium hydroxide. The aqueous phases are extracted with 3 times 10 mL of ethyl acetate. The organic phases are dried over MgSO4, filtered and concentrated under vacuum in a rotary evaporator. 65 mg of N-[3-(5-fluoro-6-perhydro-1,4-oxazepin-4-yl-1H-benzimidazol-2-yl)-1H-pyrazol-4-yl]piperidine-1-carboxamide are obtained in the form of a gray solid.

Workup

  1. concentrationThe reaction medium is concentrated under vacuum in a rotary evaporator
  2. customreacted again at 22° C. for 16 hours with 4 mL of a 4N solution of hydrochloric acid in dioxane
  3. concentrationThe reaction medium is concentrated under vacuum in a rotary evaporator
  4. customThe reaction crude
  5. customis purified by flash chromatography, elution
  6. additionbeing carried out with a mixture of cyclohexane/ethyl acetate
  7. additionThe product is diluted in ethyl acetate
  8. washwashed with 2 times 5 mL of a 2N aqueous solution of sodium hydroxide
  9. extractionThe aqueous phases are extracted with 3 times 10 mL of ethyl acetate
  10. dry with materialThe organic phases are dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated under vacuum in a rotary evaporator

Sources & evidence

ORD record
ord-6654177586c849fb95c7c0a065dbbaf3
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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