2-(4-Fluorophenyl)acetyl isothiocyanate → 1-(4-(2-Chloropyridin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)thiourea

HRID 1670220Notes

Reaction equation

HRID 1670220 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH2:15])=[CH:11][C:10]=2[F:16])[CH:5]=[CH:4][N:3]=1.[F:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25]([N:27]=[C:28]=[S:29])=[O:26])=[CH:20][CH:19]=1>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15][C:28]([NH:27][C:25](=[O:26])[CH2:24][C:21]3[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=3)=[S:29])=[CH:11][C:10]=2[F:16])[CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 231532482-(4-Fluorophenyl)acetyl isothiocyanateHCID 598529984-(2-Chloropyridin-4-yloxy)-3-fluorobenzenamine

Product 1

HCID 251970761-(4-(2-Chloropyridin-4-yloxy)-3-fluorophenyl)-3-(2-(4-fluorophenyl)acetyl)thioureaYield 64%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

4-Fluorophenylacetylchloride (Aldrich, 0.072 mL, 0.525 mmol, 2.5 eq) was added to a solution of sodium thiocyanate (0.056 g, 0.695 mmol, 3.3 eq) in ethyl acetate (2.0 mL) at room temperature and the reaction mixture was stirred for 1.5 h to afford a solution of 2-(4-fluorophenyl)ethanoyl isothiocyanate (0.263 M). A solution of 4-(2-chloropyridin-4-yloxy)-3-fluorobenzenamine (0.050 g, 0.21 mmol, 1.0 eq) in CH2Cl2 (1.0 mL) was added dropwise to the 2-(4-fluorophenyl)ethanoyl isothiocyanate solution and the reaction mixture was stirred at room temperature for 12 h. The reaction mixture was concentrated in vacuo and the resulting residue was purified by silica gel flash chromatography (Merck, 40-63 μM, 230-240 mesh, eluting 3/1 hexane/ethyl acetate) to afford the title compound (0.058 g, 64%) as a solid. 1H NMR (DMSO-d6) δ 12.46 (s, 1H), 11.84 (s, 1H), 8.35-8.33 (m, 1H), 8.02-8.33 (m, 1H), 6.99-7.52 (m, 8H), 3.84 (s, 2H); MS (ESI+) m/z 434 (M+H)+; HRMS (ESI+) calcd.: 434.0542. found: 434.0547.

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe resulting residue was purified by silica gel flash chromatography (Merck, 40-63 μM, 230-240 mesh, eluting 3/1 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-f3ada4a46a094f85a6ad7562628ed59e
Source dataset
uspto-grants-2011_08
Patent number
US07989477B2

Reaction notes

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