Tetrahydrofuran → N-[(2-Chloro-3-pyridinyl)methyl]-N′-(2,3-dichlorophenyl)thiourea

HRID 1035051Notes

Reaction equation

HRID 1035051 reaction equation
Cl.[Cl:2][C:3]1[C:8]([CH2:9][NH2:10])=[CH:7][CH:6]=[CH:5][N:4]=1.O1CCCC1.C(N(C(C)C)CC)(C)C.[Cl:25][C:26]1[C:27]([Cl:35])=[C:28]([N:32]=[C:33]=[S:34])[CH:29]=[CH:30][CH:31]=1>O>[Cl:2][C:3]1[C:8]([CH2:9][NH:10][C:33]([NH:32][C:28]2[CH:29]=[CH:30][CH:31]=[C:26]([Cl:25])[C:27]=2[Cl:35])=[S:34])=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 27962812,3-Dichlorophenyl IsothiocyanateHCID 51358205(2-chloropyridin-3-yl)methanamine hydrochloride

Product 1

HCID 86082283N-[(2-Chloro-3-pyridinyl)methyl]-N′-(2,3-dichlorophenyl)thioureaYield 47%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To an oven-dried, N2-purged, 25-mL, round-bottomed flask containing a magnetic stir bar were added the product of Example 141A, anhydrous tetrahydrofuran (5 mL), and diisopropylethylamine (646 mg, 0.886 mL, 5.00 mmol). The flask was sealed with a septum and neat dichlorophenylisothiocyanate (306 mg, 0.213 mL, 1.50 mmol) was added via syringe. The reaction mixture was stirred at room temperature overnight. Water (10 mL) was added, and the reaction was transferred to a separatory funnel. The mixture was extracted with dichloromethane (3×10 mL). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated by rotary evaporator to give a brown solid. The product was recrystallized from ethyl acetate/hexanes to give 197 mg (47%) of the title compound as a white powder. MS (ESI″) m/z 345.9 (M+H)+; 1H NMR (DMSO-d6) δ 4.75 (d, J=5.1 Hz, 2H), 7.37 (dd, J=8.0, 8.0 Hz, 1H), 7.46 (dd, J=7.5, 4.7 Hz, 1H), 7.55 (d, J=8.1 Hz, 1H), 7.61 (d, J=7.8 Hz, 1H), 7.76 (dd, J=7.6, 1.5 Hz, 1H), 8.32 (dd, J=4.7, 1.7 Hz, 1H), 8.44 (br s, 1H), 9.68 (br s, 1H).

Workup

  1. customTo an oven-dried, N2-purged
  2. addition25-mL, round-bottomed flask containing a magnetic stir bar
  3. additionwas added via syringe
  4. customthe reaction was transferred to a separatory funnel
  5. extractionThe mixture was extracted with dichloromethane (3×10 mL)
  6. dry with materialThe combined organic extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated by rotary evaporator
  9. customto give a brown solid
  10. customThe product was recrystallized from ethyl acetate/hexanes

Sources & evidence

ORD record
ord-81905bf9189f4944ab0a25ef8591a495
Source dataset
uspto-grants-2013_10
Patent number
US08546374B2

Reaction notes

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