Isopropanol → HCID 178462375, compound

HRID 1946285Notes

Reaction equation

HRID 1946285 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.CC(O)C.[C:33]([OH:38])(=[O:37])[C@H:34]([CH3:36])[OH:35]>C(OCC)(=O)C>[C:33]([OH:38])(=[O:37])[C@H:34]([CH3:36])[OH:35].[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

5

Reactant 3

HCID 3776IsopropanolHCID 107689L-Lactic AcidHCID 178522431HCID 178522431, compound

Product 1

HCID 178462375HCID 178462375, compoundYield 60.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
67.5 °C

Procedure

1-Cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea (1.859 Kg, 4.872 mol, 1.0 wt), propan-2-ol (9.00 L, 5.0 vol) and ethyl acetate (8.00 L, 4.5 vol) were charged to a flange flask equipped with a mechanical stirrer and thermometer. The contents were stirred under nitrogen and L-lactic acid (0.504 Kg, 5.59 mol, 0.269 wt) was added at 15 to 25° C. followed by a line rinse of ethyl acetate (0.90 L, 0.5 vol). The mixture was stirred at 15 to 25° C. for 120 to 140 minutes. The solid was isolated by filtration, the filter-cake washed with ethyl acetate (2×2.00 L, 2×1.0 vol) and pulled dry for 20 to 40 minutes. The filter-cake was dissolved in ethanol (33.00 L, 17.7 vol) at 75 to 85° C., cooled to 65 to 70° C. and the solution clarified through glass microfibre paper. The filtrates were cooled to and aged at 15 to 25° C. for 2 to 3 hours. The crystallised solid was isolated by filtration, the filter-cake washed with ethanol (2×1.00 L, 2×0.5 vol) and pulled dry for at least 30 minutes. The solid was 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 (1.386 Kg, 58.7% th, 99.47% by HPLC area,) as a dark pink uniform solid.

Workup

  1. customequipped with a mechanical stirrer
  2. washrinse of ethyl acetate (0.90 L, 0.5 vol)
  3. stirringThe mixture was stirred at 15 to 25° C. for 120 to 140 minutes
  4. customThe solid was isolated by filtration
  5. washthe filter-cake washed with ethyl acetate (2×2.00 L, 2×1.0 vol)
  6. custompulled dry for 20 to 40 minutes
  7. dissolutionThe filter-cake was dissolved in ethanol (33.00 L, 17.7 vol) at 75 to 85° C.
  8. temperatureThe filtrates were cooled to and
  9. customThe crystallised solid was isolated by filtration
  10. washthe filter-cake washed with ethanol (2×1.00 L, 2×0.5 vol)
  11. custompulled dry for at least 30 minutes
  12. customThe solid was dried under vacuum at 35 to 45° C.

Sources & evidence

ORD record
ord-b8a709260d3f4f72956f86a430e0888a
Source dataset
uspto-grants-2013_03
Patent number
US08399442B2

Reaction notes

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