Hydrogen Bromide → 1-N-[3-Fluoro-5-(trifluoromethyl)pyridin-2-yl]-1-methylcyclopentane-1,2-diamine

HRID 1750517Notes

Reaction equation

[F:1][C:2]1[C:3]([NH:12][C:13]2([CH3:32])[CH2:17][CH2:16][CH2:15][CH:14]2[NH:18]C(=O)O[C@@H]2C[C@H](C)CC[C@H]2C(C)C)=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.Br>C(O)(=O)C>[F:1][C:2]1[C:3]([NH:12][C:13]2([CH3:32])[CH2:17][CH2:16][CH2:15][CH:14]2[NH2:18])=[N:4][CH:5]=[C:6]([C:8]([F:11])([F:9])[F:10])[CH:7]=1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution (1R,2S,5R)-5-methyl-2-(propan-2-yl)cyclohexyl N-(2-{[3-fluoro-5-(trifluoromethyl)pyridin-2-yl]amino}-2-methylcyclopentyl)carbamate (0.533 g, 1.16 mmol) in acetic acid (4 ml) was added HBr (6 M, 0.98 ml, 5.80 mmol). The reaction was sealed and heated at 90° C. for 24 hours. To this was then added further HBr (6 M, 0.50 ml, 3.00 mmol) and the reaction was heated at 90° C. for a further 6 hours. The reaction was cooled to room temperature and concentrated in vacuo. The residue was purified by SCX chromatography (2M ammonia in methanol) and then concentrated in vacuo. The crude product was further purified by reverse phase chromatography (C18 silica, 0-100% water (with 0.05% ammonia)/acetonitrile) to afford the title compound as a single trans-enantiomer.

Workup

customThe reaction was sealed
temperaturethe reaction was heated at 90° C. for a further 6 hours
temperatureThe reaction was cooled to room temperature
concentrationconcentrated in vacuo
customThe residue was purified by SCX chromatography (2M ammonia in methanol)
concentrationconcentrated in vacuo
customThe crude product was further purified by reverse phase chromatography (C18 silica, 0-100% water (with 0.05% ammonia)/acetonitrile)

Sources & evidence

ORD record: ord-caa25a22f6a749e08148fd7df577c418
Source dataset: uspto-grants-2015_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09156829B2

Reaction notes

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