Dimethylformamide → HCID 10273888, compound

HRID 411237Notes

Reaction equation

HRID 411237 reaction equation
Br[C:2]1[S:24][C:5]2[N:6]([CH3:23])[N:7]=[C:8]([C:12]([NH:14][CH2:15][C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)=[O:13])[S:9](=[O:11])(=[O:10])[C:4]=2[CH:3]=1.CN([CH:28]=[O:29])C.[CH2:30](N(CC)CC)[CH3:31]>>[Cl:22][C:19]1[CH:20]=[CH:21][C:16]([CH2:15][NH:14][C:12]([C:8]2[S:9](=[O:11])(=[O:10])[C:4]3[CH:3]=[C:2]([C:30]#[C:31][CH2:28][OH:29])[S:24][C:5]=3[N:6]([CH3:23])[N:7]=2)=[O:13])=[CH:17][CH:18]=1

Participants

4

Reactant 3

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 22397197HCID 22397197, compound

Product 1

HCID 10273888HCID 10273888, compoundYield 25%

Conditions

Temperature
65 °C

Procedure

A solution containing the 6-bromo-N-(4-chlorobenzyl)-1-methyl-1H-thieno[2,3-e]-[1,3,4]thiadiazine-3-carboxamide 4,4-dioxide (Preparation 57, 0.19 g), DMF (6 mL), and triethylamine (0.8 mL) is degassed by evacuation under house vacuum and filling with nitrogen 3 times. To this solution is added propargyl alcohol (24 μL), palladium(II)chloride bistriphenylphosphine (8 mg), and copper(I)iodide (14 mg). The mixture is warmed to 65° C. After cooling, the reaction mixture is concentrated under a stream of nitrogen and the resulting residue is partitioned between CH2Cl2 and water. The organic layer is washed with brine, dried over Na2SO4, filtered, and concentrated to give a brown oil. The crude product is chromatographed on a Biotage column eluting with 60% ethyl acetate in heptane (200 mL), 80% ethyl acetate in heptane (200 mL), and ethyl acetate (500 mL) followed by purification by radial chromatography eluting with CH2Cl2 to give 40 mg (25%) of the title compound as a pale yellow solid. Physical characteristics: M.p. 98° C. (dec); MS (ESI+) m/z 446 (M+Na)+; HRMS (FAB) m/z 424.0191 (C17H14ClN3O4S2+H).

Workup

  1. customis degassed by evacuation under house vacuum
  2. additionTo this solution is added propargyl alcohol (24 μL), palladium(II)chloride bistriphenylphosphine (8 mg), and copper(I)iodide (14 mg)
  3. temperatureAfter cooling
  4. concentrationthe reaction mixture is concentrated under a stream of nitrogen
  5. customthe resulting residue is partitioned between CH2Cl2 and water
  6. washThe organic layer is washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto give a brown oil
  11. customThe crude product is chromatographed on a Biotage column
  12. washeluting with 60% ethyl acetate in heptane (200 mL), 80% ethyl acetate in heptane (200 mL)
  13. customethyl acetate (500 mL) followed by purification by radial chromatography
  14. washeluting with CH2Cl2

Sources & evidence

ORD record
ord-3581384c73164aafa8b128731a41fd65
Source dataset
uspto-grants-2003_05
Patent number
US06559145B2

Reaction notes

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