Potassium Fluoride → 6-Chloro-3-fluoro-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide

HRID 2268748Notes

Reaction equation

HRID 2268748 reaction equation
Cl[C:2]1[NH:7][C:6]2[CH:8]=[C:9]([Cl:11])[S:10][C:5]=2[S:4](=[O:13])(=[O:12])[N:3]=1.[F-:14].[K+]>[Br-].C([N+](C)(C)C)CCCCCCCCCCCCCCC.CN1CCCC1=O>[Cl:11][C:9]1[S:10][C:5]2[S:4](=[O:13])(=[O:12])[N:3]=[C:2]([F:14])[NH:7][C:6]=2[CH:8]=1

Participants

5

Reactant 2

HCID 522689Potassium FluorideHCID 118320583,6-Dichloro-4h-thieno[3,2-e][1,2,4]thiadiazine 1,1-dioxide

Product 1

HCID 109226916-Chloro-3-fluoro-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide

Reagents, catalysts & solvents 2

HCID 5974Hexadecyltrimethylammonium BromideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 3,6-dichloro-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide (1.02 g, 3.95 mmol), potassium fluoride (688 mg, 11.9 mmol) and hexadecyltrimethylammonium bromide (43 mg, 0.12 mmol) in dry 1-methyl-2-pyrrolidinone (4 ml) was stirred for 20 h at 130° C. under nitrogen to form 6-chloro-3-fluoro-4H-thieno[3,2-e]-1,2,4-thiadiazine 1,1-dioxide. The mixture was allowed to cool to room temperature and then reacted directly with 1-ethylcyclohexylamine hydrochloride (0.8 g, 5.93 mmol) and triethylamine (1.65 ml, 11.9 mmol) for 30 h at 75° C. in the sealed flask. The cooled mixture was poured into water, acidified to pH <2 with 1N hydrochloric acid and extracted with ethyl acetate. The organic phase was dried with sodium sulphate and evaporated to dryness to give the pure title compound; mp 244-246° C.; 1H-NMR (DMSO-d6): δ0.79 (t, 3H), 1.70-1.93 (m, 8H), 1.96-2.08 (m, 2H), 2.13-2.25 (m, 2H), 7.09 (s, 1H), 7.24 (br s, 1 H), 10.57 (br s, 1 H).

Sources & evidence

ORD record
ord-1f43de02d44a4330b15678a1360c6bd4
Source dataset
uspto-grants-2001_12
Patent number
US06329367B1

Reaction notes

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