Methylamine → HCID 86680963, compound

HRID 331499Notes

Reaction equation

[Br:1][C:2]1[N:3]=[C:4]([C:9]2[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20]Cl)=[CH:16][CH:15]=3)[CH:10]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.[CH3:22][NH2:23]>C(O)C>[Br:1][C:2]1[N:3]=[C:4]([C:9]2[O:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][NH:23][CH3:22])=[CH:16][CH:15]=3)[CH:10]=2)[C:5]([NH2:8])=[N:6][CH:7]=1

Participants

Conditions

Temperature: 70 °C

Procedure

Trifluoroacetic Acid (2.500 mL) was added to a solution of tert-butyl N-[5-bromo-3-[3-[4-(chloromethyl)phenyl]isoxazol-5-yl]pyrazin-2-yl]-N-tert-butoxycarbonyl-carbamate (500 mg, 0.8836 mmol) in dichloromethane (20.00 mL) and the mixture was stirred at ambient temperature for 10 minutes. The reaction mixture was concentrated in vacuo to give 5-bromo-3-[3-[4-(chloromethyl)phenyl]isoxazol-5-yl]pyrazin-2-amine (323.1 mg, assumed 100% yield) which was used as such in next step. LC/MS m/z 365.4 [M−H]− Step 2: 5-bromo-3-[3-[4-(chloromethyl)phenyl]isoxazol-5-yl]pyrazin-2-amine was dissolved in ethanol, methanamine in ethanol (2.495 g, 3.300 mL, 26.51 mmol) was added and the mixture was stirred at 70° C. in a microwave. The reaction mixture was concentrated in vacuo. The residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. Combined organic extract was dried (MgSO4) and concentrated in vacuo yielding 5-bromo-3-(3-(4-((methylamino)methyl)phenyl)isoxazol-5-yl)pyrazin-2-amine as an oil that was used without further purification.

Workup

concentrationThe reaction mixture was concentrated in vacuo
customThe residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate
extractionCombined organic extract
dry with materialwas dried (MgSO4)
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-c1568a49b7144f0f9993866efb629d53
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08877759B2

Reaction notes

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