Pyridine → 1,4-Dioxaspiro[4.5]decan-2-yl-1,2,4-thiadiazol-5-amine

HRID 1511028Notes

Reaction equation

[N-:1]=[C:2]=[S:3].[Na+].[N:5]1C=CC=CC=1.CS(O[N:16]=[C:17](Cl)[C@H:18]1[CH2:22][O:21][C:20]2([CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[O:19]1)(=O)=O.CC1C(OC2C(N)=NC=C(SC3C=CC=CN=3)C=2)=CC=C(C)N=1>C(#N)C>[O:19]1[C:20]2([CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]2)[O:21][CH2:22][CH:18]1[C:17]1[N:1]=[C:2]([NH2:5])[S:3][N:16]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of sodium isothiocyanate (0.24 g, 3.0 mmol) in acetonitrile (30 mL) was added pyridine (0.51 g, 6.5 mmol) followed by (R)-N-(methylsulfonyloxy)-1,4-dioxaspiro[4.5]decane-2-carbimidoyl chloride (0.77 g, 2.6 mmol) and the reaction was stirred at 60° C. for 20 minutes, followed by addition of 3-(2,6-dimethylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-amine (0.70 g, 2.2 mmol) and the reaction was stirred overnight at 60° C. The reaction was concentrated in vacuo and the residue partitioned between EtOAc and 2 M NaOH. The combined organic layers were washed with brine, dried over MgSO4 and concentrated in vacuo. The material was purified over silica gel (30% EtOAc in CH2Cl2) to afford (S)-N-(3-(2,6-dimethylpyridin-3-yloxy)-5-(pyridin-2-ylthio)pyridin-2-yl)-3-(1,4-dioxaspiro[4.5]decan-2-yl-1,2,4-thiadiazol-5-amine (0.50 g, 0.91 mmol, 42% yield).

Workup

stirringthe reaction was stirred overnight at 60° C
concentrationThe reaction was concentrated in vacuo
customthe residue partitioned between EtOAc and 2 M NaOH
washThe combined organic layers were washed with brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customThe material was purified over silica gel (30% EtOAc in CH2Cl2)

Sources & evidence

ORD record: ord-68d6c0eb37d3477b80d021e8d8cec238
Source dataset: uspto-grants-2012_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08212045B2

Reaction notes

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