Acetic Acid → HCID 178521853, compound

HRID 353436Notes

Reaction equation

HRID 353436 reaction equation
[Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:33]=[CH:32][C:8]([C:9]([CH:11]2[C:19](=[O:20])[C:18]3[C:13](=[CH:14][CH:15]=[CH:16][C:17]=3[NH:21][C:22]([NH:24][N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[O:23])[C:12]2=O)=O)=[CH:7][CH:6]=1.O.[NH2:35][NH2:36].CC(O)=O>CCO>[Cl:1][CH2:2][CH2:3][O:4][C:5]1[CH:33]=[CH:32][C:8]([C:9]2[NH:36][N:35]=[C:12]3[C:13]4[C:18]([C:19](=[O:20])[C:11]=23)=[C:17]([NH:21][C:22]([NH:24][N:25]2[CH2:30][CH2:29][O:28][CH2:27][CH2:26]2)=[O:23])[CH:16]=[CH:15][CH:14]=4)=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 24654Hydrazine hydrate (1:1)HCID 23513714HCID 23513714, compound

Product 1

HCID 178521853HCID 178521853, compoundYield 61%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a suspension of 1-{2-[4-(2-chloroethoxy)benzoyl]-1,3-dioxo-indan-4-yl}-3-morpholin-4-yl-urea (39 g, 82.6 mmol) in EtOH (425 mL) was added hydrazine monohydrate (20.7 g, 413 mmol) followed by AcOH (9.9 g, 165.3 mmol). The reaction mixture was heated at reflux for 48 h. The reaction mixture was cooled to room temp. The yellow solid was collected by filtration, rinsed with EtOH and dried under vacuum. The solid was suspended in THF (1000 mL) and 1N HCl (500 mL) was added. The resulting suspension was stirred for 90 min. Brine (500 mL) was added and the pH was adjusted to 13 with 50% NaOH. The layers were separated and the aqueous layer was washed with THF (2×300 mL). The combined organic layers were washed with 1N HCl/brine (1×250 mL, 1:1), then brine (1×250 mL), dried (MgSO4), and concentrated under reduced pressure. The yellow solid was triturated with Et2O then dried under vacuum to give the desired pyrazole (23.5 g, 61% yield).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 48 h
  3. filtrationThe yellow solid was collected by filtration
  4. washrinsed with EtOH
  5. customdried under vacuum
  6. addition1N HCl (500 mL) was added
  7. additionBrine (500 mL) was added
  8. customThe layers were separated
  9. washthe aqueous layer was washed with THF (2×300 mL)
  10. washThe combined organic layers were washed with 1N HCl/brine (1×250 mL, 1:1)
  11. dry with materialbrine (1×250 mL), dried (MgSO4)
  12. concentrationconcentrated under reduced pressure
  13. customThe yellow solid was triturated with Et2O
  14. customthen dried under vacuum

Sources & evidence

ORD record
ord-00210479db7e41f597760d49c71bb456
Source dataset
uspto-grants-2004_06
Patent number
US06753329B2

Reaction notes

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