Pyridine → N-morpholinyl-3,4-dichloro-isothiazole-5-carboxamide

HRID 382242Notes

Reaction equation

HRID 382242 reaction equation
[Cl:1][C:2]1[C:6]([Cl:7])=[C:5]([C:8](Cl)=[O:9])[S:4][N:3]=1.[NH2:11][N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1.N1C=CC=CC=1>O1CCCC1>[N:12]1([NH:11][C:8]([C:5]2[S:4][N:3]=[C:2]([Cl:1])[C:6]=2[Cl:7])=[O:9])[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1

Participants

5

Reactant 3

HCID 1049PyridineHCID 20315N-AminomorpholineHCID 109768863,4-Dichloro-5-isothiazolecarbonyl chloride

Product 1

HCID 15456851N-morpholinyl-3,4-dichloro-isothiazole-5-carboxamideYield 63.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
2.5 °C

Procedure

At 0 to 5° C. and with ice-cooling and stirring, 2.43 g (0.01 mol) of 3,4-dichloro-isothiazole-5-carbonyl chloride are added dropwise over a period of 5 minutes to a mixture of 1.21 g (0.011 mol) of 4-amino-morpholine and 22 ml of absolute pyridine. After the addition, the reaction mixture is admixed with 1.5 ml of absolute tetrahydrofuran, allowed to warm to room temperature and then stirred at room temperature for one hour. The reaction mixture is subsequently concentrated under reduced pressure. The residue that remains is admixed with 60 ml of water and 60 ml of ethyl acetate. The organic phase is separated off and the aqueous phase is extracted twice more with ethyl acetate. The combined organic phases are successively washed with 20 ml of saturated aqueous sodium bicarbonate solution and 50 ml of water, then dried over sodium sulphate and concentrated under reduced pressure. The residue is triturated in a mixture of 30 ml methylene chloride and 70 ml of petroleum ether. The resulting solid is filtered off with suction and dried. In this manner, 1.79 g (63% of theory) of N-morpholinyl-3,4-dichloro-isothiazole-5-carboxamide are obtained in the form of a solid of melting point 198 to 199° C.

Workup

  1. additionAfter the addition
  2. temperatureto warm to room temperature
  3. stirringstirred at room temperature for one hour
  4. concentrationThe reaction mixture is subsequently concentrated under reduced pressure
  5. customThe organic phase is separated off
  6. extractionthe aqueous phase is extracted twice more with ethyl acetate
  7. washThe combined organic phases are successively washed with 20 ml of saturated aqueous sodium bicarbonate solution and 50 ml of water
  8. dry with materialdried over sodium sulphate
  9. concentrationconcentrated under reduced pressure
  10. customThe residue is triturated in a mixture of 30 ml methylene chloride and 70 ml of petroleum ether
  11. filtrationThe resulting solid is filtered off with suction
  12. customdried

Sources & evidence

ORD record
ord-251a45b34f8e4c1ab42746c3c4eb80ac
Source dataset
uspto-grants-2001_10
Patent number
US06310005B1

Reaction notes

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