Sodium Carbonate → 5-(3,6-dihydro-2H-thiopyran-4-yl)pyridin-2-amine

HRID 595812Notes

Reaction equation

Br[C:2]1[CH:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=1.[S:9]1[CH2:14][CH:13]=[C:12](B2OC(C)(C)C(C)(C)O2)[CH2:11][CH2:10]1.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[S:9]1[CH2:10][CH:11]=[C:12]([C:2]2[CH:3]=[CH:4][C:5]([NH2:8])=[N:6][CH:7]=2)[CH2:13][CH2:14]1

Participants

Conditions

Temperature: 115 °C

Procedure

To a solution of 5-bromopyridin-2-amine (344 mg, 1.99 mmol) in DME (6 mL) was added 2-(3,6-dihydro-2H-thiopyran-4-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (300 mg, 1.33 mmol), and sodium carbonate (1.99 mL, 3.98 mmol). The mixture was purged with nitrogen for 5 min, and followed by the addition of PdCl2(dppf)-CH2Cl2 (108 mg, 0.13 mmol). The resulting mixture was heated to 115° C. in an oil bath for 5 h. The reaction mixture was diluted with ethyl acetate, washed with water, brine, dried and was concentrated. The residue was purified by flash column chromatography on silica gel (ISCO) eluting with 0-90% ethyl acetate in heptane to give Fractions were combined and concentrated to give 5-(3,6-dihydro-2H-thiopyran-4-yl)pyridin-2-amine (120 mg, 47%) as brown color solid. LCMS (m/z): 193 (MH+), 0.44 min.

Workup

customThe mixture was purged with nitrogen for 5 min
washwashed with water, brine
customdried
concentrationwas concentrated
customThe residue was purified by flash column chromatography on silica gel (ISCO)
washeluting with 0-90% ethyl acetate in heptane
customto give Fractions
concentrationconcentrated

Sources & evidence

ORD record: ord-d45b2d7a0f2c407184272cf4e51d7f2b
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09242996B2

Reaction notes

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