Tetrabutylammonium Fluoride → 2-(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)-2-methylpropan-1-ol

HRID 1930016Notes

Reaction equation

HRID 1930016 reaction equation
[Si]([O:8][CH2:9][C:10]([C:13]1[N:17]2[N:18]=[C:19]([C:22]3[N:26]4[CH2:27][CH2:28][CH2:29][C:25]4=[N:24][C:23]=3[C:30]3[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=3[F:37])[CH:20]=[CH:21][C:16]2=[N:15][N:14]=1)([CH3:12])[CH3:11])(C(C)(C)C)(C)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[F:37][C:31]1[CH:32]=[C:33]([F:36])[CH:34]=[CH:35][C:30]=1[C:23]1[N:24]=[C:25]2[CH2:29][CH2:28][CH2:27][N:26]2[C:22]=1[C:19]1[CH:20]=[CH:21][C:16]2[N:17]([C:13]([C:10]([CH3:12])([CH3:11])[CH2:9][OH:8])=[N:14][N:15]=2)[N:18]=1

Participants

4

Reactant 2

HCID 2724141Tetrabutylammonium FluorideHCID 579299783-(1-(tert-Butyldimethylsilyloxy)-2-methylpropan-2-yl)-6-(2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazine

Product 1

HCID 498309602-(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)-2-methylpropan-1-olYield 16%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

The 3-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-6-(2-(2,4-difluorophenyl)-6,7-dihydro-5H-pyrrolo[1,2-a]imidazol-3-yl)-[1,2,4]triazolo[4,3-b]pyridazine (0.606 g, 1.16 mmol, Preparation #E.1.1.1) was dissolved in THF (15 mL) and reacted at about ambient temperature with TBAF (1.0 M in THF, 1.39 mL, 1.39 mmol) for about 4 h. The crude reaction mixture was partitioned between water and DCM. The organics were dried over MgSO4, filtered and concentrated under reduced pressure. The resulting crude material was purified by chromatography on silica gel (DCM/MeOH gradient from 100:0-85:15) and triturated with a mixture of heptane/Et2O (90:10) to give the title compound as a yellow solid (0.074 g, 16%): LC/MS (Table 1, Method g) Rt=1.64 min.; MS m/z: 411.98 (M+H)+.

Workup

  1. customThe crude reaction mixture
  2. customwas partitioned between water and DCM
  3. dry with materialThe organics were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting crude material was purified by chromatography on silica gel (DCM/MeOH gradient from 100:0-85:15)
  7. customtriturated with a mixture of heptane/Et2O (90:10)

Sources & evidence

ORD record
ord-ae185b3e128b4768b7eb9a45c88e747d
Source dataset
uspto-grants-2012_05
Patent number
US08188083B2

Reaction notes

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