Ammonium Chloride → 3-(2,6-Dimethylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-amine

HRID 534010Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([O:9][C:10]2[C:11]([CH3:17])=[N:12][C:13]([CH3:16])=[CH:14][CH:15]=2)[C:5]([NH2:8])=[N:6][CH:7]=1.C[Li].C([Li])CCC.N1C=CC=C(S[S:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=2)C=1.[NH4+].[Cl-]>C1COCC1>[CH3:17][C:11]1[C:10]([O:9][C:4]2[C:5]([NH2:8])=[N:6][CH:7]=[C:2]([S:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][N:34]=3)[CH:3]=2)=[CH:15][CH:14]=[C:13]([CH3:16])[N:12]=1

Participants

Conditions

Temperature: -78 °C

Procedure

A 250 mL flask was charged with 5-bromo-3-(2,6-dimethylpyridin-3-yloxy)pyridin-2-amine (5.00 g, 17.66 mmol) and THF (100 mL) and purged with nitrogen. The solution was cooled to −78° C., methyl lithium (1.6 M in hexanes, 12.7 mL, 20.4 mmol) was added and the reaction was stirred for 5 minutes. Butyl lithium (2.5 M in Hexanes, 8.1 mL, 20.4 mmol) was added and the reaction was stirred for 10 minutes at −78° C. (solids formed). 2-(2-(Pyridin-3-yl)disulfanyl)pyridine (4.49 g, 20.4 mmol) was added and the reaction was warmed to ambient temperature and stirred for 18 hours. The reaction was poured into aqueous NH4Cl, extracted with EtOAc, washed with brine, dried over MgSO4 and concentrated in vacuo. The residue was purified over silica gel (5% MeOH in CH2Cl2) to afford 3-(2,6-dimethylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-amine (3.5 g, 63%).

Workup

custompurged with nitrogen
stirringthe reaction was stirred for 10 minutes at −78° C.
custom(solids formed)
temperaturethe reaction was warmed to ambient temperature
stirringstirred for 18 hours
extractionextracted with EtOAc
washwashed with brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customThe residue was purified over silica gel (5% MeOH in CH2Cl2)

Sources & evidence

ORD record: ord-30bd9a271df84625a35b0387d5e726e3
Source dataset: uspto-grants-2014_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08853409B2

Reaction notes

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