Hydrochloric Acid → HCID 178508054, compound

HRID 1639646Notes

Reaction equation

HRID 1639646 reaction equation
C(OC(=O)[NH:7][C:8]1[C:9]([C:13](=O)[NH:14][C:15]2[CH:20]=[CH:19][C:18]([CH2:21][N:22]3[CH2:27][CH2:26][O:25][CH2:24][CH2:23]3)=[CH:17][C:16]=2[NH2:28])=[N:10][NH:11][CH:12]=1)(C)(C)C.Cl.C(=O)([O-])[O-].[K+].[K+]>C(O)C>[N:22]1([CH2:21][C:18]2[CH:19]=[CH:20][C:15]3[NH:14][C:13]([C:9]4[C:8]([NH2:7])=[CH:12][NH:11][N:10]=4)=[N:28][C:16]=3[CH:17]=2)[CH2:27][CH2:26][O:25][CH2:24][CH2:23]1

Participants

5

Reactant 3

HCID 313Hydrochloric Acid2×HCID 11430Potassium CarbonateHCID 178452920HCID 178452920, compound

Product 1

HCID 178508054HCID 178508054, compoundYield 95.6%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
75 °C

Procedure

[3-(2-Amino-4-morpholin-4-ylmethyl-phenylcarbamoyl)-1H-pyrazol-4-yl]-carbamic acid tert-butyl ester (1.350 Kg, 3.24 mol, 1.0 wt) and ethanol (6.75 L, 5.0 vol) were charged to a flange flask equipped with a mechanical stirrer, condenser and thermometer. Conc. aq. hydrochloric acid (1.10 L, 13.2 mol, 0.80 vol) was added at 15 to 30° C. under nitrogen and the contents were then heated to 70 to 80° C. and maintained at this temperature for 16 to 24 hours. A second portion of hydrochloric acid (0.11 L, 1.32 mol, 0.080 vol) was added at 70 to 80° C. and the reaction was heated for a further 4 hours. Reaction completion was determined by HPLC analysis. The reaction mixture was cooled to 10 to 20° C. and potassium carbonate (1.355 Kg, 9.08 mol, 1.0 wt) was charged portionwise at this temperature. The suspension was stirred until gas evolution ceased and was then filtered. The filter-cake was washed with ethanol (1.35 L, 1.0 vol) and the filtrates retained. The filter-cake was slurried with ethanol (4.00 L, 3.0 vol) at 15 to 25° C. for 20 to 40 minutes and the mixture was filtered. The filter-cake was washed with ethanol (1.35 L, 1.0 vol) and the total combined filtrates were concentrated under vacuum at 35 to 45° C. Ethanol (4.00 L, 3.0 vol) was charged to the residue and removed under vacuum at 35 to 45° C. Tetrahydrofuran (5.90 L, 4.4 vol) was added to the residue and stirred for 10 to 20 minutes at 15 to 25° C. The resulting solution was filtered, the filter-cake was washed with tetrahydrofuran (1.35 L, 1.0 vol) and the combined filtrates were concentrated under vacuum at 35 to 45° C. Tetrahydrofuran (5.40 L, 4.0 vol) was charged to the concentrate and removed under vacuum at 35 to 45° C. Tetrahydrofuran (5.40 L, 4.0 vol) was charged to the concentrate and removed under vacuum at 35 to 45° C. to give the desired product, 3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-ylamine (0.924 Kg, 95.5%, 82.84% by HPLC area) as a purple foam.

Workup

  1. customequipped with a mechanical stirrer, condenser
  2. temperaturemaintained at this temperature for 16 to 24 hours
  3. temperaturethe reaction was heated for a further 4 hours
  4. customReaction completion
  5. temperatureThe reaction mixture was cooled to 10 to 20° C.
  6. filtrationwas then filtered
  7. washThe filter-cake was washed with ethanol (1.35 L, 1.0 vol)
  8. filtrationthe mixture was filtered
  9. washThe filter-cake was washed with ethanol (1.35 L, 1.0 vol)
  10. concentrationthe total combined filtrates were concentrated under vacuum at 35 to 45° C
  11. additionEthanol (4.00 L, 3.0 vol) was charged to the residue
  12. customremoved under vacuum at 35 to 45° C
  13. additionTetrahydrofuran (5.90 L, 4.4 vol) was added to the residue
  14. stirringstirred for 10 to 20 minutes at 15 to 25° C
  15. filtrationThe resulting solution was filtered
  16. washthe filter-cake was washed with tetrahydrofuran (1.35 L, 1.0 vol)
  17. concentrationthe combined filtrates were concentrated under vacuum at 35 to 45° C
  18. additionTetrahydrofuran (5.40 L, 4.0 vol) was charged to the
  19. concentrationconcentrate
  20. customremoved under vacuum at 35 to 45° C
  21. additionTetrahydrofuran (5.40 L, 4.0 vol) was charged to the
  22. concentrationconcentrate
  23. customremoved under vacuum at 35 to 45° C.

Sources & evidence

ORD record
ord-ec09de317d1b4a7ebb77daf83ac95070
Source dataset
uspto-grants-2012_02
Patent number
US08110573B2

Reaction notes

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