Hydrochloric Acid → HCID 67051631, compound

HRID 1672974Notes

Reaction equation

[OH:1][C:2]1([CH:13]2[CH2:18][N:17]([S:19]([C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=3[N+:28]([O-:30])=[O:29])(=[O:21])=[O:20])[CH2:16][CH2:15][NH:14]2)[CH2:5][N:4](C(OC(C)(C)C)=O)[CH2:3]1.Cl.O1CCOCC1>CO>[N+:28]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[S:19]([N:17]1[CH2:16][CH2:15][NH:14][CH:13]([C:2]2([OH:1])[CH2:5][NH:4][CH2:3]2)[CH2:18]1)(=[O:21])=[O:20])([O-:30])=[O:29]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 1,1-dimethylethyl 3-hydroxy-3-{4-[(2-nitrophenyl)sulfonyl]piperazin-2-yl}azetidine-1-carboxylate (308 mg, 0.70 mmol) in methanol (10 mL) was added HCl in dioxane (4 N, 1.75 mL, 7.0 mmol), and the mixture was heated to 60° C. for 30 minutes. The solution was concentrated to provide 3-{4-[(2-nitrophenyl)sulfonyl]piperazin-2-yl}azetidin-3-ol as a sticky white solid. This material was dissolved in dichloromethane (7 mL). To the solution was added N,N-diisopropylethylamine (1.16 mL, 7.0 mmol) followed by 3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoyl fluoride (277 mg, 0.7 mmol), prepared using procedures similar to those described in Reference 1, and the resulting mixture was stirred at room temperature for 16 hours. The solution was concentrated and the residue was purified by column chromatography (95% dichloromethane:5% methanol) to provide 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-{4-[(2-nitrophenyl)sulfonyl]piperazin-2-yl}azetidin-3-ol as a pale yellow foam (453 mg, 0.63 mmol, 90% yield). 1H NMR (400 MHz, CDCl3): 8.49 (s, 1H), 7.96 (dd, 1H), 7.71 (m, 2H), 7.53 (dd, 1H), 7.39 (dd, 1H), 7.33 (d, 1H), 7.15 (m, 1H), 6.84 (br s, 1H), 6.62 (m, 1H), 4.29-3.97 (br m, 4H), 3.79-3.62 (m, 3H), 3.26-2.99 (br m, 3H), 2.92-2.62 (br m, 3H); MS (EI) for C26H23F3IN5O6S: 718 (MH+).

Workup

concentrationThe solution was concentrated

Sources & evidence

ORD record: ord-e7db4660183c4ddfacfadbc118f93909
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07999006B2

Reaction notes

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