Toluene → HCID 67438472, compound

HRID 521368Notes

Reaction equation

HRID 521368 reaction equation
C(O[C:4]1[CH2:5][N:6]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7][CH2:8][N:9]=1)C.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([CH:24]([NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[C:25]([NH:27][NH2:28])=O)=[CH:20][CH:19]=1.C1(C)C=CC=CC=1>C(OCC)(=O)C>[C:32]([O:31][C:30]([NH:29][CH:24]([C:21]1[CH:22]=[CH:23][C:18]([Cl:17])=[CH:19][CH:20]=1)[C:25]1[N:9]2[CH2:8][CH2:7][N:6]([C:10]([O:12][C:13]([CH3:14])([CH3:15])[CH3:16])=[O:11])[CH2:5][C:4]2=[N:28][N:27]=1)=[O:36])([CH3:35])([CH3:33])[CH3:34]

Participants

5

Reactant 3

HCID 1140TolueneHCID 67437264HCID 67437264, compoundHCID 67439401tert-butyl 3-ethoxy-5,6-dihydropyrazine-1(2H)-carboxylate

Product 1

HCID 67438472HCID 67438472, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A solution of tert-butyl 3-ethoxy-5,6-dihydropyrazine-1(2H)-carboxylate (0.762 g, 3.34 mmol) and tert-butyl 1-(4-chlorophenyl)-2-hydrazinyl-2-oxoethylcarbamate (1.00 g, 3.34 mmol) in toluene (6.67 mL, 3.34 mmol) was heated to reflux and stirred at this temperature for 1 hour. The reaction mixture was cooled to room temperature, diluted with ethyl acetate, and washed with water. The organic layer was dried and concentrated to give a residue that was purified by reverse phase chromatography (Biotage SP4, 40+M, C18, 10% to 100% ACN/H2O) to afford tert-butyl 3-((tert-butoxycarbonylamino)(4-chlorophenyl)methyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazine-7(8H)-carboxylate (0.92 g, 60%). LCMS (APCI+) M+H+: 463 (25%), 464 (90%), 466 (25%), 467 (5%); rt=3.56 minutes. 1H NMR (400 MHz, CDCl3) δ □7.33 (d, J=8.6 Hz, 1H), 7.29 (d, J=8.6 Hz, 1H), 6.12 (d, J=7.8 Hz, 1H), 5.87 (d, J=7.8 Hz, 1H), 4.84 (d, J=17.6 Hz, 1H), 4.75 (d, J=17.6 Hz, 1H), 3.93 (m, 1H), 3.80 (m, 1H), 3.73 (m, 1H), 3.49 (m, 1H), 1.47 (s, 9H), 1.41 (s, 9H).

Workup

  1. temperatureto reflux
  2. washwashed with water
  3. customThe organic layer was dried
  4. concentrationconcentrated
  5. customto give a residue that
  6. customwas purified by reverse phase chromatography (Biotage SP4, 40+M, C18, 10% to 100% ACN/H2O)

Sources & evidence

ORD record
ord-4720302c1f8c4ffaa359a06adfe8d315
Source dataset
uspto-grants-2016_05
Patent number
US09328091B2

Reaction notes

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