Hydroxylamine → HCID 136395915, compound

HRID 1854392Notes

Reaction equation

HRID 1854392 reaction equation
[S:1]([N:11]1[C:15]2=[N:16][CH:17]=[C:18]([CH:20]=O)[N:19]=[C:14]2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2].[NH2:22][OH:23]>CO>[S:1]([N:11]1[C:15]2=[N:16][CH:17]=[C:18]([CH:20]=[N:22][OH:23])[N:19]=[C:14]2[CH:13]=[CH:12]1)([C:4]1[CH:10]=[CH:9][C:7]([CH3:8])=[CH:6][CH:5]=1)(=[O:3])=[O:2]

Participants

4

Reactant 2

HCID 787HydroxylamineHCID 580098835-tosyl-5H-pyrrolo[2,3-b]pyrazine-2-carbaldehyde

Product 1

HCID 136395915HCID 136395915, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
45 °C

Procedure

To a solution of 5-tosyl-5H-pyrrolo[2,3-b]pyrazine-2-carbaldehyde (0.150 g, 0.498 mmol) in MeOH (10 mL) was added hydroxylamine (50% solution in water, 0.061 mL, 1.0 mmol). The reaction mixture was heated to about 45° C. After about 2 h, the reaction mixture was cooled to ambient temperature and concentrated under reduced pressure to provide the crude 5-tosyl-5H-pyrrolo[2,3-b]pyrazine-2-carbaldehyde oxime as a tan solid. LC/MS (Table 2, Method a) Rt=2.15 min; MS m/z: 317 (M+H)+. To a solution of the crude oxime in THF (20 mL) was added AcOH (0.285 mL, 4.98 mmol) followed by zinc dust (<10 micron, 0.130 g, 1.99 mmol). After a further 2 h, additional AcOH (0.285 mL, 4.98 mmol) and zinc dust (<10 micron, 0.130 g, 1.99 mmol) were added to the reaction mixture. After about an additional 2 h, additional AcOH (0.285 mL, 4.98 mmol) and zinc dust (<10 micron, 0.130 g, 1.99 mmol) were added to the reaction mixture. After about 15 h, the reaction mixture was diluted with DCM (about 5 mL) and filtered. The filtrate was washed with saturated aqueous NaHCO3 and brine. The organic layer was dried over anhydrous Na2SO4, filtered, treated with HCl (4 M in 1,4-dioxane, 1 mL) and concentrated under reduced pressure to provide (5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine hydrochloride: LC/MS (Table 2, Method a) Rt=1.64 min; MS m/z: 303 (M+H)+. To a suspension of the crude amine hydrochloride in DCM (10 mL) was added TEA (0.208 mL, 1.49 mmol) followed by cyclohexanecarbonyl chloride (0.101 mL, 0.747 mmol). After about 30 min, the reaction mixture was diluted with DCM and washed with saturated aqueous NaHCO3 (25 mL) and brine (25 mL). The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude amide was purified by silica gel chromatography eluting with a gradient of 40-80% EtOAc in DCM to provide N-((5-tosyl-5H-pyrrolo[2,3-b]pyrazin-2-yl)methyl)cyclohexanecarboxamide as a tan solid (0.081 g, 39% over 2 steps). LC/MS (Table 2, Method a) Rt=2.40 min; MS m/z: 413 (M+H)+.

Workup

  1. temperaturethe reaction mixture was cooled to ambient temperature
  2. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-b9b074fe64e0447eb9d3616dc6617790
Source dataset
uspto-grants-2015_02
Patent number
US08962629B2

Reaction notes

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