Tetrahydrofuran → 1-(6-(2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethanone

HRID 1930081Notes

Reaction equation

HRID 1930081 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[CH2:30][CH2:29][CH2:28][N:12]2[C:13]=1[C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:20]([C:23]([O:25]CC)=O)=[N:21][N:22]=2)[N:19]=1.[CH2:31]1COCC1.C[Mg]Cl>O.C(Cl)Cl.[Cl-].[NH4+]>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[N:10]=[C:11]2[CH2:30][CH2:29][CH2:28][N:12]2[C:13]=1[C:14]1[CH:15]=[CH:16][C:17]2[N:18]([C:20]([C:23](=[O:25])[CH3:31])=[N:21][N:22]=2)[N:19]=1

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 57929901Ethyl 6-(2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylateHCID 178418332HCID 178418332, compound

Product 1

HCID 579298461-(6-(2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)ethanoneYield 97%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 25517Ammonium ChlorideSolvent2×

Procedure

A 100 mL round bottom flask was charged with ethyl 6-(2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazine-3-carboxylate (3.04 g, 7.41 mmol). THF (37.0 mL) was added and the mixture was stirred at ambient temperature for about 15 min. The slurry was cooled to about −40° C. and a solution of methylmagnesium chloride (3 M in THF, 9.88 mL, 29.6 mmol) was added slowly while keeping the internal temperature between about −30° C. and −40° C. After about 15 min the mixture was cooled to about −55° C. followed by the slow addition of saturated ammonium chloride solution (about 10 mL). The mixture was then warmed to ambient temperature and diluted with water (50 mL), DCM (75 mL), and saturated aqueous ammonium chloride solution (50 mL). The layers were separated and the aqueous solution was extracted with DCM (2×100 mL). The combined organic extracts were dried over MgSO4, filtered, and concentrated under reduced pressure to give the title compound (2.74 g, 97%): LC/MS (Table 1, Method h) Rt=1.22 min; MS m/z: 381.1 (M+H)+.

Workup

  1. temperatureThe slurry was cooled to about −40° C.
  2. customthe internal temperature between about −30° C. and −40° C
  3. temperatureAfter about 15 min the mixture was cooled to about −55° C.
  4. temperatureThe mixture was then warmed to ambient temperature
  5. customThe layers were separated
  6. extractionthe aqueous solution was extracted with DCM (2×100 mL)
  7. dry with materialThe combined organic extracts were dried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-87aede87a2164889aee8d3a0450020b5
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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