Hydroxyamine hydrochloride → 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-hydroxyimino-cyclohexyl)-N-pyrazin-2-yl-propionamide

HRID 2214136Notes

Reaction equation

Cl.[NH2:2][OH:3].[Cl:4][C:5]1[CH:6]=[C:7]([CH:15]([CH2:25][CH:26]2[CH2:31][CH2:30][C:29](=O)[CH2:28][CH2:27]2)[C:16]([NH:18][C:19]2[CH:24]=[N:23][CH:22]=[CH:21][N:20]=2)=[O:17])[CH:8]=[CH:9][C:10]=1[S:11]([CH3:14])(=[O:13])=[O:12]>CO.N1C=CC=CC=1>[Cl:4][C:5]1[CH:6]=[C:7]([CH:15]([CH2:25][CH:26]2[CH2:31][CH2:30][C:29](=[N:2][OH:3])[CH2:28][CH2:27]2)[C:16]([NH:18][C:19]2[CH:24]=[N:23][CH:22]=[CH:21][N:20]=2)=[O:17])[CH:8]=[CH:9][C:10]=1[S:11]([CH3:14])(=[O:13])=[O:12]

Participants

Conditions

Temperature: 25 °C

Procedure

A solution of hydroxylamine hydrochloride (19 mg, 0.27 mmol) in methanol (0.5 mL) and pyridine (0.5 mL) was treated with 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-oxo-cyclohexyl)-N-pyrazin-2-yl-propionamide (prepared as in Example 58, 80 mg, 0.18 mmol). The reaction mixture was heated under reflux for 2 h, cooled to 25° C., and concentrated in vacuo to remove methanol. The resulting residue was suspended in ethyl acetate (10 mL), washed with water (1×5 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 12M, Silica, 35/65 hexanes/ethyl acetate to 1/1 hexanes/ethyl acetate) afforded 2-(3-chloro-4-methanesulfonyl-phenyl)-3-(4-hydroxyimino-cyclohexyl)-N-pyrazin-2-yl-propionamide (65 mg, 80%) was a white foam: EI-HRMS m/e calcd for C20H23ClN4O4S (M+H)+ 451.1202, found 451.1206.

Workup

temperatureThe reaction mixture was heated
temperatureunder reflux for 2 h
concentrationconcentrated in vacuo
customto remove methanol
washwashed with water (1×5 mL)
dry with materialdried over magnesium sulfate
filtrationfiltered
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-994abd7f1e5647b5bc26df32f78977e9
Source dataset: uspto-grants-2006_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07105671B2

Reaction notes

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