Benzoyl chloride, 3-chloro- → 6-[4-[5-(3-Chlorophenyl)-1,2,4-oxadiazol-3-yl]piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine

HRID 1674994Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5](Cl)=[O:6].O[NH:12][C:13]([N:15]1[CH2:20][CH2:19][N:18]([C:21]2[CH:22]=[CH:23][C:24]3[N:25]([C:27]([C:30]([F:33])([F:32])[F:31])=[N:28][N:29]=3)[N:26]=2)[CH2:17][CH2:16]1)=[NH:14].CCN(C(C)C)C(C)C>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]2[O:6][N:14]=[C:13]([N:15]3[CH2:16][CH2:17][N:18]([C:21]4[CH:22]=[CH:23][C:24]5[N:25]([C:27]([C:30]([F:33])([F:32])[F:31])=[N:28][N:29]=5)[N:26]=4)[CH2:19][CH2:20]3)[N:12]=2)[CH:8]=[CH:9][CH:10]=1

Participants

Conditions

Temperature: 150 °C

Procedure

3-Chlorobenzoyl chloride (92 mg, 0.53 mmol) was added to a stirred partial solution of N-hydroxy-4-[3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl]piperazine-1-carboximidamide (165 mg, 0.5 mmol) and DIPEA (97 mg, 0.75 mmol) in THF (3 mL). The reaction mixture became a clear solution over 30 minutes and LCMS after 1 hour showed complete initial acylation. The reaction mixture was heated at 150° C. for 15 minutes by microwave after which LCMS showed complete cyclisation to the desired product. The reaction mixture was evaporated and the residue was boiled briefly with ethanol, cooled and filtered off to give 6-[4-[5-(3-chlorophenyl)-1,2,4-oxadiazol-3-yl]piperazin-1-yl]-3-(trifluoromethyl)[1,2,4]triazolo[4,3-b]pyridazine (104 mg, 46%) as a crystalline powder.

Workup

customover 30 minutes

Sources & evidence

ORD record: ord-1caba17b6a3a400baf8bca5012137c66
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08003649B2

Reaction notes

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