Acetyl chloride → 1-(3-(3-(2,4-Difluorophenyl)-4-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-1H-pyrazol-1-yl)pyrrolidin-1-yl)ethanone

HRID 1929997Notes

Reaction equation

HRID 1929997 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:13]([C:14]2[CH:15]=[CH:16][C:17]3[N:18]([C:20]([CH:23]([CH3:25])[CH3:24])=[N:21][N:22]=3)[N:19]=2)=[CH:12][N:11]([CH:26]2[CH2:30][CH2:29][NH:28][CH2:27]2)[N:10]=1.CCN(C(C)C)C(C)C.[C:40](Cl)(=[O:42])[CH3:41]>C(Cl)Cl>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:13]([C:14]2[CH:15]=[CH:16][C:17]3[N:18]([C:20]([CH:23]([CH3:24])[CH3:25])=[N:21][N:22]=3)[N:19]=2)=[CH:12][N:11]([CH:26]2[CH2:30][CH2:29][N:28]([C:40](=[O:42])[CH3:41])[CH2:27]2)[N:10]=1

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 579298656-(3-(2,4-Difluorophenyl)-1-(pyrrolidin-3-yl)-1H-pyrazol-4-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine

Product 1

HCID 579299381-(3-(3-(2,4-Difluorophenyl)-4-(3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-1H-pyrazol-1-yl)pyrrolidin-1-yl)ethanoneYield 84.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a round bottom flask was added 6-(3-(2,4-difluorophenyl)-1-(pyrrolidin-3-yl)-1H-pyrazol-4-yl)-3-isopropyl-[1,2,4]triazolo[4,3-b]pyridazine (0.150 g, 0.366 mmol, Example #Q.1.1.1), DCM (10 mL), DIPEA (0.077 mL, 0.440 mmol) and acetyl chloride (0.029 mL, 0.403 mmol). The reaction mixture was stirred at ambient temperature for about 10 min. The reaction mixture was diluted with DCM (50 mL) and washed with saturated aqueous NaHCO3 (50 mL), dried with MgSO4, filtered and concentrated in vacuo. The crude material was purified by flash chromatography (40 g RediSep® silica gel; DCM/MeOH gradient from 1:0 to 9:1) to give the title compound (0.140 g, 84%): LC/MS (Table 1, Method g) Rt=2.07 min; MS m/z: 452.4 (M+H)+.

Workup

  1. washwashed with saturated aqueous NaHCO3 (50 mL)
  2. dry with materialdried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude material was purified by flash chromatography (40 g RediSep® silica gel; DCM/MeOH gradient from 1:0 to 9:1)

Sources & evidence

ORD record
ord-f9efffe579174a81bcb19f4e80129da1
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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