Triphenyl phosphite → (S)-methyl 4-isopropyl-3-methyl-2-oxo-1,2,3,4-tetrahydropyrido[3,2-b]pyrazine-7-carboxylate

HRID 69606

Reaction equation

HRID 69606 reaction equation
C([O:3][C:4](=O)[C@@H:5]([N:7]([CH:21]([CH3:23])[CH3:22])[C:8]1[C:17]([N+:18]([O-])=O)=[CH:16][C:11]([C:12]([O:14][CH3:15])=[O:13])=[CH:10][N:9]=1)[CH3:6])C.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1>ClCCl.[NH4+].[O-][V](=O)=O.[Pt]>[CH:21]([N:7]1[C@@H:5]([CH3:6])[C:4](=[O:3])[NH:18][C:17]2[CH:16]=[C:11]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=[N:9][C:8]1=2)([CH3:23])[CH3:22]

Participants

6

Reactant 2

HCID 7540Triphenyl phosphiteHCID 58324420(S)-methyl 6-((1-ethoxy-1-oxopropan-2-yl)(isopropyl)amino)-5-nitronicotinate

Product 1

HCID 59416799(S)-methyl 4-isopropyl-3-methyl-2-oxo-1,2,3,4-tetrahydropyrido[3,2-b]pyrazine-7-carboxylateYield 94.3%

Reagents, catalysts & solvents 3

HCID 23939PlatinumCatalystHCID 516859Ammonium metavanadateCatalystHCID 6344DichloromethaneSolvent

Procedure

(S)-methyl 6-((1-ethoxy-1-oxopropan-2-yl)(isopropyl)amino)-5-nitronicotinate (0.900 g, 2.65 mmol) was dissolved in dichloromethane (10 mL). To this solution was added triphenyl phosphite (3.0 mg, 9.7 umol), ammonium metavanadate (30 mg, 0.265 mmol) and Pt/C (5% wt., 0.120 g). The reaction mixture was hydrogenated at 80 psi at 25° C. for 6 h. The mixture was filtered through a small pad of celite and the pad was washed with dichloromethane (20 mL). The combined filtrates were concentrated in vacuo and crystallized with ethyl ether to afford the title compounds as a white solid (0.658 g, 94%). 1H NMR (400 MHz, CHLOROFORM-d) δ (ppm): 1.33 (d, J=6.82 Hz, 3 H) 1.36-1.41 (m, 6 H) 3.90 (s, 3 H) 4.34 (q, J=6.65 Hz, 1 H) 4.86 (m, 1 H) 7.52 (d, J=1.77 Hz, 1 H) 8.59 (d, J=1.77 Hz, 1 H) 8.73 (br. s., 1 H); [M+H] calc'd for C13H17N3O3, 264; found, 264.

Workup

  1. filtrationThe mixture was filtered through a small pad of celite
  2. washthe pad was washed with dichloromethane (20 mL)
  3. concentrationThe combined filtrates were concentrated in vacuo
  4. customcrystallized with ethyl ether

Sources & evidence

ORD record
ord-54c36d5df05246269b0dc9e22713aeea
Source dataset
uspto-grants-2014_09
Patent number
US08822470B2

Linked notes

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