Sulfuric Acid → HCID 86707768, compound

HRID 2410114Notes

Reaction equation

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

Participants

Conditions

Temperature: 110 °C

Procedure

To a stirred solution of 2-bromo-5-[(4-chloro-phenyl)-hydroxy-methyl]-1-cyclobutyl-1H-imidazole-4-carboxylic acid (3-chloro-4-fluoro-phenyl)-amide (step AK1; 0.470 g, 0.907 mmol) and AcOH (4.53 ml) was added H2SO4 98% (0.592 ml, 10.88 mmol). The solution was stirred for 7 h at 110° C. The reaction mixture was concentrated in vacuo. The residue was neutralized with 1M NaHCO3 and extracted with EtOAc (2×). The organic phases were washed with brine and dried (Na2SO4), filtered and concentrated. The residue was purified by flash chromatography (hexane/EtOAc, 1:1), then triturated in diisopropyl ether/hexane to afford the title compound. tR: 1.29 min (LC-MS 2); ESI-MS: 496.0 [M+H]+ (LC-MS 2); 1H-NMR (DMSO-d6, 400 MHz) δ ppm 7.79 (m, 1H), 7.49 (m, 1H), 7.38 (s, 4H), 7.35 (m, 1H), 6.89 (s, 1H), 4.73 (m, 1H), 2.45 (m, 2H), 1.86 (m, 1H), 1.63 (m, 1H), 1.42 (m, 2H).

Workup

concentrationThe reaction mixture was concentrated in vacuo
extractionextracted with EtOAc (2×)
washThe organic phases were washed with brine
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe residue was purified by flash chromatography (hexane/EtOAc, 1:1)
customtriturated in diisopropyl ether/hexane

Sources & evidence

ORD record: ord-03819f35c0304ad087c01eeed33a0e91
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08815926B2

Reaction notes

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