4-Fluorophenyl isocyanate → N-(4-fluorophenyl)-2-[3-(trifluoromethyl)-[1,2,4]triazolo[3,4-f]pyridazin-6-yl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxamide

HRID 1674973Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]=[O:10])=[CH:4][CH:3]=1.[CH2:11]1[CH:15]2[CH2:16][NH:17][CH2:18][CH:14]2[CH2:13][N:12]1[C:19]1[CH:20]=[CH:21][C:22]2[N:23]([C:25]([C:28]([F:31])([F:30])[F:29])=[N:26][N:27]=2)[N:24]=1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([N:17]2[CH2:16][CH:15]3[CH2:11][N:12]([C:19]4[CH:20]=[CH:21][C:22]5=[N:27][N:26]=[C:25]([C:28]([F:31])([F:29])[F:30])[N:23]5[N:24]=4)[CH2:13][CH:14]3[CH2:18]2)=[O:10])=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 70 °C

Procedure

1-Fluoro-4-isocyanatobenzene (0.026 g, 0.19 mmol) was added to a suspension of 6-(hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-3-(trifluoromethyl)-[1,2,4]triazolo[4,3-b]pyridazine (0.05 g, 0.17 mmol) in toluene (1.5 mL). The reaction mixture was heated at 70° C. for 1 hour and evaporated to give an involatile residue. The residue was purified by hplc using a Phenomenex Luna C18 100A column (10μ 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 N-(4-fluorophenyl)-2-[3-(trifluoromethyl)-[1,2,4]triazolo[3,4-f]pyridazin-6-yl]-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrole-5-carboxamide (0.0309 g, 42%) as a white solid.

Workup

customevaporated
customto give an involatile residue
customThe residue was purified by hplc
washeluted with decreasingly polar mixtures of water (containing 0.1% trifluoroacetic acid) and acetonitrile as eluents

Sources & evidence

ORD record: ord-9e3352cde6f84eb592727b59b3487ed6
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08003649B2

Reaction notes

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