Hydrochloric Acid → 7-Methyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,5]benzodiazepin-6(7h)-one

HRID 80501Notes

Reaction equation

HRID 80501 reaction equation
[O:1]=[C:2]1[NH:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[N:5]2[CH2:13][CH2:14][N:15](C(OC(C)(C)C)=O)[CH2:16][CH:4]2[CH2:3]1.[H-].[Na+].[CH3:26]I.Cl>CN(C)C=O>[CH3:26][N:8]1[C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[N:5]2[CH2:13][CH2:14][NH:15][CH2:16][CH:4]2[CH2:3][C:2]1=[O:1]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 58284919tert-butyl 6-oxo-1,2,4a,5,6,7-hexahydropyrazino[1,2-a][1,5]benzodiazepine-3(4H)-carboxylate

Product 1

HCID 497644147-Methyl-1,2,3,4,4a,5-hexahydropyrazino[1,2-a][1,5]benzodiazepin-6(7h)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of Example 1C (50 mg, 0.16 mmol) in N,N-dimethylformamide (1 mL) was added sodium hydride (65%, 6.98 mg, 0.19 mmol). The solution was allowed to stir at room temperature for 1 hour before addition of methyl iodide (11.77 μL, 0.19 mmol). The reaction mixture was stirred overnight. The solution was concentrated, and dichloromethane (1 mL) was added followed by HCl (4M in dioxane, 394 μL, 1.6 mmol). After reaction completion as indicated by LC/MS analysis, the solution was concentrated and purified by preparative HPLC to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 7.35 (d, J=7.80 Hz, 1H), 7.13-7.30 (m, 3H), 3.32-3.47 (m, 3H), 3.17-3.32 (m, 5H) 2.89-3.15 (m, 2H), 2.62 (dd, J=13.22, 7.12 Hz, 1H), 2.12 (d, J=13.56 Hz, 1H); MS (ESI) m/z 231.9 (M+H)+.

Workup

  1. concentrationThe solution was concentrated
  2. additiondichloromethane (1 mL) was added
  3. customAfter reaction completion
  4. concentrationthe solution was concentrated
  5. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-11735958c1be4d638a112dcc585b1a1f
Source dataset
uspto-grants-2014_09
Patent number
US08846663B2

Reaction notes

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