Chlorosuccinimide → 6-bromo-5-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine

HRID 1623314Notes

Reaction equation

[Br:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:5]=[CH:4][CH:3]=1.C1C(=O)N([Cl:23])C(=O)C1>C(#N)C>[Br:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)[CH:5]=[CH:4][C:3]=1[Cl:23]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 6-bromo-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine (20 g, 74 mmol) in acetonitrile (240 mL) was added NCS (9.85 g, 74 mmol). The mixture was heated to 80° C. for 3 hr. The reaction mixture was allowed to cool to ambient temperature and concentrated in vacuo. The resulting residue was diluted with brine (200 mL) and extracted with EtOAc (3×200 mL). The combined organic layers were concentrated in vacuo. The resulting residue was purified by column chromatography [SiO2, EtOAc/heptane=0/100 to 50/50] providing 6-bromo-5-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine (12 g) and a mixture of 6-bromo-3,5-dichloro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine/6-bromo-3-chloro-N-((tetrahydro-2H-pyran-4-yl)methyl)pyridin-2-amine (5 g, ratio ˜2:3).

Workup

temperatureto cool to ambient temperature
concentrationconcentrated in vacuo
additionThe resulting residue was diluted with brine (200 mL)
extractionextracted with EtOAc (3×200 mL)
concentrationThe combined organic layers were concentrated in vacuo
customThe resulting residue was purified by column chromatography [SiO2, EtOAc/heptane=0/100 to 50/50]

Sources & evidence

ORD record: ord-78a90d4a5ced48799ed49d52dba0d8e9
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08778951B2

Reaction notes

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