Triphenyl phosphite → (S)-3-bromo-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-one

HRID 716346

Reaction equation

HRID 716346 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([N+:18]([O-])=O)[C:5]([N:8]2[CH2:12][CH2:11][CH2:10][C@H:9]2[C:13](OCC)=[O:14])=[N:6][CH:7]=1.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>ClCCl.[NH4+].[O-][V](=O)=O.[Pt]>[Br:1][C:2]1[CH:7]=[N:6][C:5]2[N:8]3[CH2:12][CH2:11][CH2:10][C@H:9]3[C:13](=[O:14])[NH:18][C:4]=2[CH:3]=1

Participants

6

Reactant 2

HCID 7540Triphenyl phosphiteHCID 58324356(S)-ethyl 1-(5-bromo-3-nitropyridin-2-yl)pyrrolidine-2-carboxylate

Product 1

HCID 58324379(S)-3-bromo-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-oneYield 42.8%

Reagents, catalysts & solvents 3

HCID 23939PlatinumCatalystHCID 516859Ammonium metavanadateCatalystHCID 6344DichloromethaneSolvent

Procedure

(S)-ethyl 1-(5-bromo-3-nitropyridin-2-yl)pyrrolidine-2-carboxylate (8.6 g, 24.99 mmol) was dissolved in dichloromethane (Volume: 125 ml) and to this solution was added triphenyl phosphite (0.078 g, 0.250 mmol), ammonium metavanadate (0.175 g, 1.499 mmol) and Pt/C (5% wt.) (0.975 g, 0.250 mmol). The reaction mixture was hydrogenated at 80 psi at 25° C. for 4 h. The reaction mixture was filtered through celite using DCM and MeOH to complete the transfer and wash the celite plug. The combined filtrates and washes were concentrated in vacuo and crystallized with ethyl ether (75 mL). The precipitate was filtered and dried in vacuum to afford (S)-3-bromo-6a,7,8,9-tetrahydropyrido[3,2-e]pyrrolo[1,2-a]pyrazin-6(5H)-one (2.87 g, 10.70 mmol, 42.8% yield) as a pale beige solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.82-2.03 (m, 3H) 2.11-2.26 (m, 1H) 3.27-3.47 (m, 1H) 3.49-3.63 (m, 1H) 4.01-4.11 (m, 1H) 7.06 (d, J=2.27 Hz, 1H) 7.77 (d, J=2.02 Hz, 1H) 10.57 (s, 1H). [M+H] calc'd for C10H10BrN3O, 268. found, 268.

Workup

  1. filtrationThe reaction mixture was filtered through celite
  2. washwash the celite plug
  3. concentrationThe combined filtrates and washes were concentrated in vacuo
  4. customcrystallized with ethyl ether (75 mL)
  5. filtrationThe precipitate was filtered
  6. customdried in vacuum

Sources & evidence

ORD record
ord-c95cfe3210444a5b9d36536428391755
Source dataset
uspto-grants-2015_11
Patent number
US09187497B2

Linked notes

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