Ammonia → 1150620-46-4

HRID 1259312Notes

Reaction equation

HRID 1259312 reaction equation
[NH3:1].[C:2]([C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:14]([C:15]3[N:20]=[C:19]([C:21]([O:23]C)=O)[C:18](=[O:25])[N:17]([C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:34])[F:33])[CH:27]=4)[C:16]=3[CH3:36])=[CH:13][CH:12]=[N:11]2)=[CH:6][CH:5]=1)#[N:3]>CO>[C:2]([C:4]1[CH:5]=[CH:6][C:7]([N:10]2[C:14]([C:15]3[N:20]=[C:19]([C:21]([NH2:1])=[O:23])[C:18](=[O:25])[N:17]([C:26]4[CH:31]=[CH:30][CH:29]=[C:28]([C:32]([F:35])([F:33])[F:34])[CH:27]=4)[C:16]=3[CH3:36])=[CH:13][CH:12]=[N:11]2)=[CH:8][CH:9]=1)#[N:3]

Participants

4

Reactant 2

HCID 222AmmoniaHCID 58432783HCID 58432783, compound

Product 1

HCID 687520991150620-46-4Yield 87%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Ammonia solution (1.12 L, 7M in MeOH, 10 eq) was added to methyl 6-[1-(4-cyanophenyl)-1H-pyrazol-5-yl]-5-methyl-3-oxo-4-[3-(trifluoromethyl)phenyl]-3,4-dihydropyrazine-2-carboxylate (377 g) and MeOH (3.8 L, 10 vols) under nitrogen. The suspension was stirred at ambient temperature for 36 h. The mixture was then filtered, washed with MeOH (2×754 ml) and dried under vacuum. The crude material was dissolved in acetone (10.7 L) at 45° C., and filtered to remove particulates. The filtrate was is concentrated to a volume of about 3.8 L. The resulting slurry was diluted by the addition of methyl isobutyl ketone (10 L), and a further 3.2 L of solvent were removed by distillation. Further methyl isobutyl ketone (7.8 L) was added to achieve a total of about 53 relative volumes (with respect to substrate). The resulting slurry was heated to 53-60° C. and held within this temperature range until in-processes testing (DSC) showed that the desired polymorph had been achieved (62 hours for this particular batch). The slurry was cooled to 25° C. over 4 hours, and then held at 20-25° C. for 36 hours. The product was collected by filtration, and the cake washed with methyl isobutyl ketone (1.9 L). The cake was dried in a vacuum oven at 55° C. until constant weight was achieved. After drying, the title compound (310.8 g, 87%) was obtained as a pale yellow crystalline solid.

Workup

  1. filtrationThe mixture was then filtered
  2. washwashed with MeOH (2×754 ml)
  3. customdried under vacuum
  4. dissolutionThe crude material was dissolved in acetone (10.7 L) at 45° C.
  5. filtrationfiltered
  6. customto remove particulates
  7. concentrationThe filtrate was is concentrated to a volume of about 3.8 L
  8. additionThe resulting slurry was diluted by the addition of methyl isobutyl ketone (10 L)
  9. customa further 3.2 L of solvent were removed by distillation
  10. additionFurther methyl isobutyl ketone (7.8 L) was added
  11. temperatureThe resulting slurry was heated to 53-60° C.
  12. custom62 hours
  13. temperatureThe slurry was cooled to 25° C. over 4 hours
  14. waitheld at 20-25° C. for 36 hours
  15. filtrationThe product was collected by filtration
  16. washthe cake washed with methyl isobutyl ketone (1.9 L)
  17. customThe cake was dried in a vacuum oven at 55° C. until constant weight
  18. customAfter drying

Sources & evidence

ORD record
ord-3d4e934e393f404da8cc094bc2b2a46c
Source dataset
uspto-grants-2013_06
Patent number
US08466284B2

Reaction notes

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