Thiophosgene → 2-(4-Isothiocyanatophenoxy)-3-(2-methylpyridin-4-yl)pyridine

HRID 410181Notes

Reaction equation

HRID 410181 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([C:8]2[C:9]([O:14][C:15]3[CH:20]=[CH:19][C:18]([NH2:21])=[CH:17][CH:16]=3)=[N:10][CH:11]=[CH:12][CH:13]=2)[CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[C:28](Cl)(Cl)=[S:29]>C(Cl)(Cl)Cl>[N:21]([C:18]1[CH:17]=[CH:16][C:15]([O:14][C:9]2[C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([CH3:1])[CH:7]=3)=[CH:13][CH:12]=[CH:11][N:10]=2)=[CH:20][CH:19]=1)=[C:28]=[S:29]

Participants

5

Reactant 3

HCID 10040ThiophosgeneHCID 10340Sodium CarbonateHCID 593271474-(3-(2-Methylpyridin-4-yl)pyridin-2-yloxy)benzenamine

Product 1

HCID 866418102-(4-Isothiocyanatophenoxy)-3-(2-methylpyridin-4-yl)pyridine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a 15 mL round bottomed flask was added 4-(3-(2-methylpyridin-4-yl)pyridin-2-yloxy)benzenamine (0.0978 g, 0.35 mmol) and sodium carbonate (0.0823 g, 0.78 mmol) in chloroform. Thiophosgene (0.030 mL, 0.39 mmol) was slowly added and allowed to stir overnight. The solution was filtered and concentrated to give 2-(4-isothiocyanatophenoxy)-3-(2-methylpyridin-4-yl)pyridine. To the flask was then added 1,2-phenylenediamine (0.0470 g, 0.410 mmol), and N,N′-dicyclohexylcarbodiimide (0.1032 g, 0.5200 mmol) in tetrahydrofuran at 75° C. to stir overnight. Upon completion, the solvent was evaporated. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Biotage™ pre-packed silica gel column (25M), eluting with a gradient of 1% to 5% methanol in DCM, to provide N-(4-(3-(2-methylpyridin-4-yl)pyridin-2-yloxy)phenyl)-1H-benzo[d]imidazol-2-amine. MS (ESI, pos. ion) m/z: 394.1 (M+1). IC50 (uM) +++++.

Workup

  1. filtrationThe solution was filtered
  2. concentrationconcentrated

Sources & evidence

ORD record
ord-3b393ff306f64100a9774d7cf3d00374
Source dataset
uspto-grants-2014_06
Patent number
US08759532B2

Reaction notes

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