Diisopropylethylamine → tert-butyl 6-oxo-1,2,4a,5,6,7-hexahydropyrazino[1,2-a][1,5]benzodiazepine-3(4H)-carboxylate

HRID 2279217Notes

Reaction equation

HRID 2279217 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[N+:20]([O-])=O)[CH:10]([CH2:23][C:24]([OH:26])=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CO.[Pd]>[O:26]=[C:24]1[NH:20][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[N:11]2[CH2:12][CH2:13][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:9][CH:10]2[CH2:23]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 58284935HCID 58284935, compound

Product 1

HCID 58284919tert-butyl 6-oxo-1,2,4a,5,6,7-hexahydropyrazino[1,2-a][1,5]benzodiazepine-3(4H)-carboxylate

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 887MethanolSolvent

Procedure

The product of Example 22C (658 mg, 1.801 mmol) was dissolved in methanol (50 mL) and 10% Pd/C (52 mg) was added. The flask was evacuated and purged with nitrogen (3 cycles) and then with hydrogen (3 cycles), and the reaction was stirred at room temperature under hydrogen (1 atm) for 7 hours. The flask was evacuated and purged with nitrogen (3 cycles), and the reaction mixture was filtered through a pad of diatomaceous earth. The filtrate was concentrated under vacuum, and the residue was dissolved in tetrahydrofuran (25 mL). O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (680 mg, 1.788 mmol) and diisopropylethylamine (1 mL) were added, and the mixture was stirred at room temperature for 14 hours and then concentrated under vacuum. The residue was purified by chromatography (SiO2, eluted with hexanes-ethyl acetate, 100:0-50:50) to provide the title compound: 1H NMR (300 MHz, CDCl3) δ ppm 1.48 (s, 9H), 2.18 (d, J=13.5 Hz, 1H), 2.74 (dd, J=13.3, 6.9 Hz, 1H), 2.88-3.30 (m, 5H), 4.01-4.19 (m, 2H), 6.93-6.98 (m, 1H), 7.01-7.10 (m, 2H), 7.16 (s, 1H), 7.17-7.24 (m, 1H); MS (DCI) m/z 318 (M+H)+.

Workup

  1. customThe flask was evacuated
  2. custompurged with nitrogen (3 cycles)
  3. customThe flask was evacuated
  4. custompurged with nitrogen (3 cycles)
  5. filtrationthe reaction mixture was filtered through a pad of diatomaceous earth
  6. concentrationThe filtrate was concentrated under vacuum
  7. dissolutionthe residue was dissolved in tetrahydrofuran (25 mL)
  8. stirringthe mixture was stirred at room temperature for 14 hours
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified by chromatography (SiO2, eluted with hexanes-ethyl acetate, 100:0-50:50)

Sources & evidence

ORD record
ord-216353619f4c49eb8469ed75da5f492a
Source dataset
uspto-grants-2015_09
Patent number
US09133206B2

Reaction notes

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