Dimethyl Sulfoxide → HCID 86755421, compound

HRID 1108564Notes

Reaction equation

HRID 1108564 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:15]2[CH2:19][CH:18]([CH2:20][NH:21]C(=O)C)[O:17][N:16]=2)[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:13][CH2:12][S:11](=[O:14])[CH2:10][CH2:9]1.O.NN.CS(C)=O>[Cl-].[Na+]>[F:1][C:2]1[CH:3]=[C:4]([C:15]2[CH2:19][CH:18]([CH2:20][NH2:21])[O:17][N:16]=2)[CH:5]=[CH:6][C:7]=1[N:8]1[CH2:9][CH2:10][S:11](=[O:14])[CH2:12][CH2:13]1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 24654Hydrazine hydrate (1:1)HCID 9950432HCID 9950432, compound

Product 1

HCID 86755421HCID 86755421, compoundYield 104.4%

Reagents, catalysts & solvents 1

HCID 5234Sodium ChlorideSolvent

Conditions

Temperature
130 °C

Procedure

423 mg (1.0 mmole) of N-({3-[3-fluoro-4-(1-oxo-1lambda4,4-thiazinan-4-yl)phenyl}-4,5-dihydro-5-isoxazolyl}methyl)acetamide is combined with 1.5 ml hydrazine hydrate and 1.5 ml dimethylsulfoxide in a 15 ml screw cap pressure tube. The reaction is heated to 130° C. for 24 hours. The mixture is cooled to room temperature, is diluted with 25 ml 50% saturated sodium chloride, and is extracted with 5×20 ml 5% methanol/chloroform. The organics are dried over potassium carbonate and are concentrated in vacuo to give 325 mg (87%) of N-({3-[3-fluoro-4-(1-oxo-1lambda4,4-thiazinan-4-yl)phenyl}-4,5-dihydro-5-isoxazolyl}methyl)amine. The crude solid, 315 mg (1.01 mmole) is dissolved in 10 ml 1:1 dichloromethane/tetrahydrofuran in an oven dried 50 ml two neck round bottom flask under nitrogen. The solution is treated with triethylamine (0.28 ml, 2.02 mmole) followed by ethyl dithioacetate (0.23 ml, 2.02 mmole) and the reaction is stirred 1 hour at room temperature. The suspension is brought to homogeneity with chloroform, is treated with 4 g silica gel (230-400 mesh), and is concentrated to dryness. The plug is chromatographed over 30 g silica gel (230-400 mesh) eluting with 2% methanol/dichloromethane for a 350 ml forerun followed by 3% methanol/dichloromethane while collecting 50 ml fractions. Fractions 2-5 are combined and concentrated to provide 277 mg (75%) of the title compouns as solid. mP=199° C.

Workup

  1. customscrew cap pressure tube
  2. temperatureThe mixture is cooled to room temperature
  3. extractionis extracted with 5×20 ml 5% methanol/chloroform
  4. dry with materialThe organics are dried over potassium carbonate
  5. concentrationare concentrated in vacuo

Sources & evidence

ORD record
ord-a100512cfffc4bc9a2241fa2627c70ee
Source dataset
uspto-grants-2000_05
Patent number
US06069141

Reaction notes

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