Hydrochloric Acid → HCID 178464313, compound

HRID 2274411Notes

Reaction equation

HRID 2274411 reaction equation
[CH2:1]([N:3]([CH2:35][CH3:36])[C:4]([NH:6][C:7]1[C:8]([C:18]2[NH:22][C:21]3[CH:23]=[C:24]([N:28]4[CH2:34][CH2:33][CH2:32][O:31][CH2:30][CH2:29]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].Cl>O1CCOCC1.C(OC(C)C)(C)C>[CH2:35]([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]([N:28]4[CH2:34][CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)[C:25]([F:27])=[CH:26][C:20]=3[N:19]=2)=[N:9][NH:10][CH:11]=1)=[O:5])[CH3:36]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 178464302HCID 178464302, compound

Product 1

HCID 178464313HCID 178464313, compoundYield 72.8%

Reagents, catalysts & solvents 2

HCID 7914Diisopropyl EtherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
22 °C

Procedure

A solution of 380 mg of 1,1-diethyl-3-[3-(5-fluoro-6-perhydro-1,4-oxazepin-4-yl-1H-benzimidazol-2-yl)-1-(tetrahydropyran-2-yl)-1H-pyrazol-4-yl]urea in solution in 5 mL of a 4N solution of hydrochloric acid in dioxane is stirred at 22° C. for 2 hours. The reaction medium is concentrated under vacuum in a rotary evaporator, and then again reacted at 22° C. for 16 hours with 5 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 diluted in ethyl acetate, and washed with 2 times 20 mL of a 2N aqueous solution of sodium hydroxide. The aqueous phases are extracted with 3 times 20 mL of ethyl acetate. The organic phases are dried over MgSO4, filtered and concentrated under vacuum in a rotary evaporator. The yellow foam obtained is made into a paste in isopropyl ether, triturated, filtered and dried under vacuum at 40° C. 230 mg of 1,1-diethyl-3-[3-(5-fluoro-6-perhydro-1,4-oxazepin-4-yl-1H-benzimidazol-2-yl)-1H-pyrazol-4-yl]urea are obtained in the form of a pale yellow solid. 1H NMR (500 MHz, DMSO-d6, δ in ppm): 1.23 (t, J=7.0 Hz, 6H); 1.96 (m, 2H); 3.35 (m masked, 4H); 3.39 (q partially masked, J=7.0 Hz, 4H); 3.79 (m, 4H); from 6.98 to 7.39 (broad m, 2H); 7.98 (s, 1H); 9.87 (broad s, 1H).

Workup

  1. concentrationThe reaction medium is concentrated under vacuum in a rotary evaporator
  2. customagain reacted at 22° C. for 16 hours with 5 mL of a 4N solution of hydrochloric acid in dioxane
  3. concentrationThe reaction medium is concentrated under vacuum in a rotary evaporator
  4. additionThe product is diluted in ethyl acetate
  5. washwashed with 2 times 20 mL of a 2N aqueous solution of sodium hydroxide
  6. extractionThe aqueous phases are extracted with 3 times 20 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 yellow foam obtained
  11. customtriturated
  12. filtrationfiltered
  13. customdried under vacuum at 40° C

Sources & evidence

ORD record
ord-b9a772e3f00c4b52bbe6b0dbbd19a103
Source dataset
uspto-grants-2015_09
Patent number
US09126969B2

Reaction notes

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