Diisopropylethylamine → 6-(5-Benzyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl)-3-(trifluoromethyl)-[1,2,4]triazolo[3,4-f]pyridazine

HRID 1674969Notes

Reaction equation

HRID 1674969 reaction equation
Cl.[CH2:2]([N:9]1[CH2:16][CH:15]2[CH:11]([CH2:12][NH:13][CH2:14]2)[CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C(N(C(C)C)CC)(C)C.Cl[C:27]1[CH:32]=[CH:31][C:30]2=[N:33][N:34]=[C:35]([C:36]([F:39])([F:38])[F:37])[N:29]2[N:28]=1>C(O)C>[CH2:2]([N:9]1[CH2:10][CH:11]2[CH2:12][N:13]([C:27]3[CH:32]=[CH:31][C:30]4=[N:33][N:34]=[C:35]([C:36]([F:39])([F:37])[F:38])[N:29]4[N:28]=3)[CH2:14][CH:15]2[CH2:16]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 6136576-Chloro-3-(trifluoromethyl)-(1,2,4)triazolo(4,3-b)pyridazineHCID 67339779HCID 67339779, compound

Product 1

HCID 673412436-(5-Benzyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl)-3-(trifluoromethyl)-[1,2,4]triazolo[3,4-f]pyridazineYield 83%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

2-Benzyl-3,3a,4,5,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrole hydrochloride (0.129 g, 0.54 mmol) and then diisopropylethylamine (0.070 g, 0.54 mmol) were added sequentially to a solution of 6-chloro-3-(trifluoromethyl)-[1,2,4]triazolo[3,4-f]pyridazine (0.080 g, 0.36 mmol) in ethanol (2 mL). The reaction mixture was heated at 70° C. for 4 hours and then evaporated to leave an involatile residue. The residue was purified by preparative hplc using a Phenomenex Luna C18 100A column (10% silica, 21 mm diameter, 150 mm length) eluted with decreasingly polar mixtures of water (containing 0.1% trifluoroacetic acid) and acetonitrile as eluents to give a partially purified product that was further purified by ion exchange chromatography an SCX column eluted with 7M aqueous ammonia in methanol as eluents to give 6-(5-benzyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-2-yl)-3-(trifluoromethyl)-[1,2,4]triazolo[3,4-f]pyridazine (0.116 g, 83%) as a white solid.

Workup

  1. customevaporated
  2. customto leave an involatile residue
  3. customThe residue was purified by preparative hplc
  4. washeluted with decreasingly polar mixtures of water (containing 0.1% trifluoroacetic acid) and acetonitrile as eluents
  5. customto give a partially purified product that
  6. customwas further purified by ion exchange chromatography an SCX column
  7. washeluted with 7M aqueous ammonia in methanol as eluents

Sources & evidence

ORD record
ord-067ca90a634e4eb79edb46e732204a18
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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