L-Lactic Acid → HCID 178462375, compound

HRID 1946287Notes

Reaction equation

HRID 1946287 reaction equation
[CH:1]1([NH:4][C:5]([NH:7][C:8]2[C:9]([C:13]3[NH:17][C:16]4[CH:18]=[CH:19][C:20]([CH2:22][N:23]5[CH2:28][CH2:27][O:26][CH2:25][CH2:24]5)=[CH:21][C:15]=4[N:14]=3)=[N:10][NH:11][CH:12]=2)=[O:6])[CH2:3][CH2:2]1.[C:29]([OH:34])(=[O:33])[C@H:30]([CH3:32])[OH:31]>C(O)C>[C:29]([OH:34])(=[O:33])[C@H:30]([CH3:32])[OH:31].[CH:1]1([NH:4][C:5]([NH:7][C:8]2[C:9]([C:13]3[NH:17][C:16]4[CH:18]=[CH:19][C:20]([CH2:22][N:23]5[CH2:24][CH2:25][O:26][CH2:27][CH2:28]5)=[CH:21][C:15]=4[N:14]=3)=[N:10][NH:11][CH:12]=2)=[O:6])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 107689L-Lactic AcidHCID 178522431HCID 178522431, compound

Product 1

HCID 178462375HCID 178462375, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
20 °C

Procedure

1-Cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea (1.0 wt), in a Class 2 or Class 3 solvent, in particular a Class 3 solvent such as aqueous ethanol (5.0-10.0 vol), can be charged to a flange flask equipped with a mechanical stirrer and thermometer. The contents are stirred under an inert atmosphere e.g. nitrogen and L-lactic acid (0.269 wt) can be added at 15 to 25° C. followed by a line rinse of the appropriate solvent such as aqueous ethanol (0.5 vol). The mixture can be stirred at 15 to 25° C. for 120 to 140 minutes. The solid may be isolated by filtration or by use of addition of anti-solvent such as n-butanol to bring the salt out of solution and then isolated by filtration. The filter-cake can be washed with the appropriate solvent (2×1.0 vol) and pulled dry for 20 to 40 minutes. The filter-cake can then be dissolved in a Class 2 or Class 3 solvent, or mixture thereof, in particular a Class 3 solvent (˜3-60 vol) at 40 to 150° C., cooled to 40 to 70° C. and the solution clarified through glass microfibre paper. The filtrates can be cooled to and aged at 15 to 25° C. for 2 to 3 hours. The crystallised solid can be isolated by filtration, the filter-cake washed with the appropriate solvent (2×0.5-2 vol) and pulled dry for at least 30 minutes. The solid can then be dried under vacuum at 35 to 45° C. to yield 1-cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea L-lactic acid salt. In addition, alternative methods of purification aside from recrystallisation may be employed for purification of the product such as flash column chromatography or filtration through a plug of silica gel or reverse-phase silica gel.

Workup

  1. customequipped with a mechanical stirrer
  2. additioncan be added at 15 to 25° C.
  3. washrinse of the appropriate solvent such as aqueous ethanol (0.5 vol)
  4. customThe solid may be isolated by filtration or by use of addition of anti-solvent such as n-butanol
  5. customisolated by filtration
  6. filtrationThe filter-cake can
  7. washbe washed with the appropriate solvent (2×1.0 vol)
  8. custompulled dry for 20 to 40 minutes
  9. filtrationThe filter-cake can
  10. dissolutionthen be dissolved in a Class 2 or Class 3 solvent, or mixture
  11. temperaturein particular a Class 3 solvent (˜3-60 vol) at 40 to 150° C., cooled to 40 to 70° C.
  12. temperatureThe filtrates can be cooled to and
  13. waitaged at 15 to 25° C. for 2 to 3 hours
  14. customThe crystallised solid can be isolated by filtration
  15. washthe filter-cake washed with the appropriate solvent (2×0.5-2 vol)
  16. custompulled dry for at least 30 minutes
  17. customThe solid can then be dried under vacuum at 35 to 45° C.

Sources & evidence

ORD record
ord-533eefae6aa44d9a88dc3530600cb9a0
Source dataset
uspto-grants-2013_03
Patent number
US08399442B2

Reaction notes

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