Water → 2-[4-Chloro-5-phenyl-3-(trifluoromethyl)pyrazolo[3,4-c]pyridazin-1-yl]-1-pyrrolidin-1-yl-ethanone

HRID 588588Notes

Reaction equation

HRID 588588 reaction equation
[H-].[Na+].[Cl:3][C:4]1[C:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)=[N:8][N:7]=[C:6]2[NH:16][N:17]=[C:18]([C:19]([F:22])([F:21])[F:20])[C:5]=12.Cl[CH2:24][C:25]([N:27]1[CH2:31][CH2:30][CH2:29][CH2:28]1)=[O:26].O>CN(C=O)C.C(Cl)Cl>[Cl:3][C:4]1[C:9]([C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=2)=[N:8][N:7]=[C:6]2[N:16]([CH2:24][C:25]([N:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)=[O:26])[N:17]=[C:18]([C:19]([F:22])([F:20])[F:21])[C:5]=12

Participants

7

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 884401-(Chloroacetyl)pyrrolidineHCID 86717288CID 86717288

Product 1

HCID 867172892-[4-Chloro-5-phenyl-3-(trifluoromethyl)pyrazolo[3,4-c]pyridazin-1-yl]-1-pyrrolidin-1-yl-ethanoneYield 14.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

Sodium hydride (18 mg, 0.45 mmol) was added to a solution of 4-chloro-5-phenyl-3-(trifluoromethyl)-1H-pyrazolo[3,4-c]pyridazine (115 mg, 0.38 mmol) and 2-chloro-1-pyrrolidin-1-yl-ethanone (81 mg, 0.55 mmol) in dry DMF (1.5 ml) and the reaction stirred for 21 h. Water and CH2Cl2 where added and the aqueous phase was extracted with CH2Cl2. The organic phases where combined, dried over MgSO4, filtered and evaporated. The residue was purified by column chromatography (silica gel, ethyl acetate/isohexane 2:8 to 1:0) followed by preparative HPLC yielding Compound Iaa as a white solid (23 mg).

Workup

  1. extractionthe aqueous phase was extracted with CH2Cl2
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by column chromatography (silica gel, ethyl acetate/isohexane 2:8 to 1:0)

Sources & evidence

ORD record
ord-bb455252fea34fda80cd8a3a506dd730
Source dataset
uspto-grants-2016_01
Patent number
US09227976B2

Reaction notes

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