Hydrochloric Acid → HCID 54671153, compound

HRID 2279242Notes

Reaction equation

HRID 2279242 reaction equation
[O:1]=[C:2]1[NH:8][CH2:7][C:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=2[N:4]2[CH2:13][CH2:14][N:15](C(OC(C)(C)C)=O)[CH2:16][CH:3]12.[H-].[Na+].Br[CH2:27][CH:28]1[CH2:30][CH2:29]1.Cl>CN(C)C=O.O1CCOCC1>[CH:28]1([CH2:27][N:8]2[CH2:7][C:6]3[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=3[N:4]3[CH2:13][CH2:14][NH:15][CH2:16][CH:3]3[C:2]2=[O:1])[CH2:30][CH2:29]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 81503BromomethylcyclopropaneHCID 54671245HCID 54671245, compound

Product 1

HCID 54671153HCID 54671153, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of tert-butyl 5-oxo-1,2,4a,5,6,7-hexahydropyrazino[1,2-a][1,4]benzodiazepine-3(4H)-carboxylate (100 mg, 0.315 mmol, Example 1) in anhydrous N,N-dimethylformamide (2 mL) was added sodium hydride (13.86 mg, 0.347 mmol). After stirring for 1 hour at room temperature, (bromomethyl)cyclopropane (102 mg, 0.756 mmol) was added to the reaction mixture. The reaction was stirred for 20 hours. The reaction was then quenched carefully with water and extracted with ethyl acetate. The organic layer was separated, dried with MgSO4, and concentrated. The residue was purified via flash chromatography (0-40% ethyl acetate/hexanes). The material obtained was dissolved in 1,4-dioxane (0.8 mL) and 4 M HCl in 1,4-dioxane (0.8 mL). The mixture was stirred for 20 hours. at room temperature. The title compound was collected by filtration as the hydrochloric acid salt. 1H NMR (500 MHz, DMSO-d6) δ 9.44 (s, 1H), 8.19 (s, 1H), 7.07-6.94 (m, 1H), 6.89 (d, J=7.9 Hz, 1H), 6.70 (t, J=7.2 Hz, 1H), 4.73 (d, J=16.0 Hz, 1H), 4.43 (s, 1H), 4.17 (d, J=16.1 Hz, 1H), 3.51-2.79 (m, 8H), 0.66 (m, 1H), 0.15-0.05 (m, 1H), 0.05-−0.08 (m, J=4.1 Hz, 1H); MS (DCI) m/z 221.1 (M+H)+.

Workup

  1. stirringThe reaction was stirred for 20 hours
  2. customThe reaction was then quenched carefully with water
  3. extractionextracted with ethyl acetate
  4. customThe organic layer was separated
  5. dry with materialdried with MgSO4
  6. concentrationconcentrated
  7. customThe residue was purified via flash chromatography (0-40% ethyl acetate/hexanes)
  8. customThe material obtained
  9. stirringThe mixture was stirred for 20 hours
  10. customat room temperature
  11. filtrationThe title compound was collected by filtration as the hydrochloric acid salt

Sources & evidence

ORD record
ord-8467121e8fac4143a42c6142872fcbd0
Source dataset
uspto-grants-2015_09
Patent number
US09133206B2

Reaction notes

Loading…