Methanesulfonyl chloride → HCID 86707735, compound

HRID 877426Notes

Reaction equation

HRID 877426 reaction equation
[C:1]1([C:7]2[CH:21]=[CH:20][C:10]3[N:11]=[C:12]([CH2:14][C:15]([O:17][CH2:18][CH3:19])=[O:16])[S:13][C:9]=3[CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C1CCN2C(=NCCC2)CC1.[CH3:33][S:34](Cl)(=[O:36])=[O:35]>CN(C=O)C>[CH3:33][S:34]([CH:14]([C:12]1[S:13][C:9]2[CH:8]=[C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH:21]=[CH:20][C:10]=2[N:11]=1)[C:15]([O:17][CH2:18][CH3:19])=[O:16])(=[O:36])=[O:35]

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chloride2×HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 58470454HCID 58470454, compound

Product 1

HCID 86707735HCID 86707735, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

Ethyl 2-(6-phenylbenzo[d]thiazol-2-yl)acetate (described in WO2011/074560, 550 mg, 1.9 mmol) was dissolved in DMF (10 mL) and cooled to 0° C. DBU (0.61 mL, 4.1 mmol) was added. After 10 minutes, methanesulfonyl chloride (0.2 mL, 3 mmol) was added dropwise. The reaction mixture was removed from the ice bath and stirred at room temperature. After 4 hours, the reaction mixture was cooled back to 0° C., and additional methane sulfonyl chloride (0.11 mL, 1.4 mmol) was added. Following addition, the reaction mixture was removed from ice bath and stirred at room temperature. After 3 days, the reaction mixture was quenched by the addition of water (20 mL), and the resulting solid was collected by filtration. The solids were dissolved in DCM, washed with aqueous 10% LiCl, 1N HCl, brine, dried over MgSO4, concentrated under reduced pressure, and purified by silica gel chromatography (eluting with 0-20% DCM/MeOH) to give Compound B1a (250 mg, 36% yield) as a yellow oil. HPLC: RT=1.03 min (LCMS Method O). MS (ES): m/z=376.0 [M+H]+. 1H NMR (400 MHz, pyridine-d5) δ 8.07 (br. s., 1H), 7.79-7.64 (m, 4H), 7.51 (t, J=7.7 Hz, 2H), 7.40 (s, 1H), 4.39 (d, J=7.0 Hz, 2H), 3.49 (s, 3H), 1.29 (t, J=7.0 Hz, 3H).

Workup

  1. customThe reaction mixture was removed from the ice bath
  2. waitAfter 4 hours
  3. temperaturethe reaction mixture was cooled back to 0° C.
  4. additionaddition
  5. customthe reaction mixture was removed from ice bath
  6. stirringstirred at room temperature
  7. waitAfter 3 days
  8. customthe reaction mixture was quenched by the addition of water (20 mL)
  9. filtrationthe resulting solid was collected by filtration
  10. dissolutionThe solids were dissolved in DCM
  11. washwashed with aqueous 10% LiCl, 1N HCl, brine
  12. dry with materialdried over MgSO4
  13. concentrationconcentrated under reduced pressure
  14. custompurified by silica gel chromatography (eluting with 0-20% DCM/MeOH)
  15. customto give Compound B1a (250 mg, 36% yield) as a yellow oil

Sources & evidence

ORD record
ord-e607576697b541b28c57fbc340b41fde
Source dataset
uspto-grants-2015_03
Patent number
US08987314B2

Reaction notes

Loading…