Sodium Chloride → HCID 178522431, compound

HRID 1946288Notes

Reaction equation

HRID 1946288 reaction equation
[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]3[C:18](=[CH:19][CH:20]=2)[N:17]=[C:16]2[N:11]3[C:12](=[O:24])[NH:13][C:14]3[C:15]2=[N:21][NH:22][CH:23]=3)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH:25]1([NH2:28])[CH2:27][CH2:26]1.[Cl-].[Na+]>CN1CCCC1=O>[CH:25]1([NH:28][C:12]([NH:13][C:14]2[C:15]([C:16]3[NH:17][C:18]4[CH:19]=[CH:20][C:8]([CH2:7][N:1]5[CH2:2][CH2:3][O:4][CH2:5][CH2:6]5)=[CH:9][C:10]=4[N:11]=3)=[N:21][NH:22][CH:23]=2)=[O:24])[CH2:27][CH2:26]1

Participants

5

Reactant 3

HCID 5234Sodium ChlorideHCID 69828CyclopropylamineHCID 178518660HCID 178518660, compound

Product 1

HCID 178522431HCID 178522431, compound

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent2×

Conditions

Temperature
100 °C

Procedure

7-Morpholin-4-ylmethyl-2,4-dihydro-1,2,4,5a,10-pentaaza-cyclopenta[a]fluoren-5-one (1.0 wt, prepared as outlined above in Example 66A) and 1-methyl-2-pyrrolidinone (3.0 vol) are charged to a suitably sized flange flask equipped with a mechanical stirrer, condenser and thermometer. Cyclopropylamine (0.351 wt) is added at 15 to 30° C. under nitrogen. The contents are then heated to 95 to 105° C. and stirred at this temperature until the reaction is judged complete by 1H NMR analysis. Once complete, the reaction mixture is cooled to 16 to 25° C. and added slowly (approximately 2 to 3 hours) to stirred ca. 13% w/w sodium chloride solution (11.5 vol) whilst maintaining the mixture at 16 to 25° C. A precipitate is formed. The transfer of the reaction mixture is completed with a 1-methyl-2-pyrrolidinone (0.5 vol) rinse at 16 to 25° C. The precipitated solid is collected by filtration, washed with water (0.5 vol) and pulled dry on the filter until deemed suitable for handling. The solid is suspended in ethyl acetate (5.0 vol) and water (6.0 vol) and stirred at 16 to 25° C. for 60 to 70 minutes. The solid is collected by filtration, sequentially washed with ethyl acetate (1.0 vol) and mixed heptanes (2×2.0 vol) and dried on the filter until deemed suitable for handling. The solid is suspended in ethyl acetate (4.0 vol) and stirred at 15 to 25° C. for at least 60 minutes. The solid is collected by filtration, washed with ethyl acetate (1.0 vol) and pulled dry on the filter to yield crude 1-cyclopropyl-3-[3-(5-morpholin-4-ylmethyl-1H-benzoimidazol-2-yl)-1H-pyrazol-4-yl]-urea (60 to 80% w/w) as a dark brown/red solid.

Workup

  1. customequipped with a mechanical stirrer, condenser
  2. temperatureOnce complete, the reaction mixture is cooled to 16 to 25° C.
  3. additionadded slowly (approximately 2 to 3 hours)
  4. temperaturewhilst maintaining the mixture at 16 to 25° C
  5. customA precipitate is formed
  6. washrinse at 16 to 25° C
  7. filtrationThe precipitated solid is collected by filtration
  8. washwashed with water (0.5 vol)
  9. custompulled dry on the
  10. filtrationfilter
  11. stirringwater (6.0 vol) and stirred at 16 to 25° C. for 60 to 70 minutes
  12. filtrationThe solid is collected by filtration
  13. washsequentially washed with ethyl acetate (1.0 vol)
  14. additionmixed heptanes (2×2.0 vol)
  15. customdried on the
  16. filtrationfilter
  17. stirringstirred at 15 to 25° C. for at least 60 minutes
  18. filtrationThe solid is collected by filtration
  19. washwashed with ethyl acetate (1.0 vol)
  20. custompulled dry on the
  21. filtrationfilter

Sources & evidence

ORD record
ord-9a1bda81099e4b12af3c11fcc20e6b92
Source dataset
uspto-grants-2013_03
Patent number
US08399442B2

Reaction notes

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