N,N'-Dimethylethylenediamine → (2-Bromo-4-fluoro-6-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1 (9),2 (7),3-trien-5-yl}phenyl)methyl acetate

HRID 1919166Notes

Reaction equation

HRID 1919166 reaction equation
[C:1]12[CH2:13][CH2:12][CH2:11][CH2:10][C:9]=1[S:8][C:7]1[C:6](=[O:14])[NH:5][N:4]=[CH:3][C:2]2=1.[C:15]([O:18][CH2:19][C:20]1[C:25]([Br:26])=[CH:24][C:23]([F:27])=[CH:22][C:21]=1Br)(=[O:17])[CH3:16].CNCCNC.C([O-])([O-])=O.[Cs+].[Cs+]>[Cu]I.O1CCOCC1>[C:15]([O:18][CH2:19][C:20]1[C:21]([N:5]2[C:6](=[O:14])[C:7]3[S:8][C:9]4[CH2:10][CH2:11][CH2:12][CH2:13][C:1]=4[C:2]=3[CH:3]=[N:4]2)=[CH:22][C:23]([F:27])=[CH:24][C:25]=1[Br:26])(=[O:17])[CH3:16]

Participants

7

Reactant 4

HCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 670165536,7,8,9-Tetrahydrobenzo[4,5]thieno[2,3-d]pyridazin-4(3H)-oneHCID 670165932,6-Dibromo-4-fluorobenzyl acetate

Product 1

HCID 58044224(2-Bromo-4-fluoro-6-{6-oxo-8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1 (9),2 (7),3-trien-5-yl}phenyl)methyl acetateYield 20%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer was charged with 8-thia-4,5-diazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3-trien-6-one (1 g, 4.85 mmol), 2,6-dibromo-4-fluorobenzyl acetate 197c (4.8 g, 14.6 mmol), copper(I) iodide (553 mg, 2.9 mmol), N1,N2-dimethylethane-1,2-diamine (512 mg, 5.82 mmol), Cs2CO3 (3.2 g, 9.7 mmol), and 1,4-dioxane (50 mL). The system was evacuated and then refilled with N2. A reflux condenser was attached to the flask, and the reaction mixture was heated at 100° C. for 16 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by flash column chromatography eluting with 5:1 petroleum ether/ethyl acetate to afford 341a as a yellow solid (437 mg, 20%). MS: [M+H]+ 451.

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer
  2. customThe system was evacuated
  3. additionrefilled with N2
  4. customA reflux condenser was attached to the flask
  5. temperatureIt was then cooled to room temperature
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated under reduced pressure
  8. customthe resulting residue was purified by flash column chromatography
  9. washeluting with 5:1 petroleum ether/ethyl acetate

Sources & evidence

ORD record
ord-a824064fba9044e39b418fac687f643b
Source dataset
uspto-grants-2013_12
Patent number
US08618107B2

Reaction notes

Loading…