Methanol → Methyl 8-(4-(tert-butoxycarbonyl)piperazin-1-yl)-[1,2,4]triazolo[4,3-a]pyrazine-5-carboxylate

HRID 1045714Notes

Reaction equation

HRID 1045714 reaction equation
Br[C:2]1[N:7]2[CH:8]=[N:9][N:10]=[C:6]2[C:5]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[N:4][CH:3]=1.C(N(CC)C(C)C)(C)C.[CH3:33]O.[C]=O.[C:37]([O-:40])(O)=[O:38].[Na+]>[Cu]I.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:20]([O:19][C:17]([N:14]1[CH2:15][CH2:16][N:11]([C:5]2[C:6]3[N:7]([CH:8]=[N:9][N:10]=3)[C:2]([C:37]([O:40][CH3:33])=[O:38])=[CH:3][N:4]=2)[CH2:12][CH2:13]1)=[O:18])([CH3:23])([CH3:22])[CH3:21]

Participants

8

Reactant 5

HCID 887MethanolHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 58447004Tert-butyl 4-(5-bromo-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylateHCID 178418416HCID 178418416, compound

Product 1

HCID 58447003Methyl 8-(4-(tert-butoxycarbonyl)piperazin-1-yl)-[1,2,4]triazolo[4,3-a]pyrazine-5-carboxylateYield 73%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
100 °C

Procedure

A 300 mL pressure vessel was charged with tert-butyl 4-(5-bromo-[1,2,4]triazolo[4,3-a]pyrazin-8-yl)piperazine-1-carboxylate (prepared as described in Example 1 steps 1-4, 10.0 g, 26 mmol), CuI (1.5 g, 7.8 mmol), Pd(dppf)Cl2 (6.4 g, 7.8 mmol), N,N-diisopropylethylamine (10 mL) and MeOH (100 mL). The vessel was charged with carbon monoxide (3.5 bar) and the reaction mixture was magnetically stirred at 100° C. for 12 h. Work-up: after the reaction mixture was cooled to room temperature, the vessel was opened. The reaction solution was diluted with saturated aqueous NaHCO3 (100 mL) and extracted with EtOAc (200 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel with 2% MeOH in CH2Cl2, to afford 7.0 g (73%) of the product as a white solid. MS m/z: 363 (M+H+).

Workup

  1. temperatureafter the reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc (200 mL×3)
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash column chromatography on silica gel with 2% MeOH in CH2Cl2

Sources & evidence

ORD record
ord-98e441e2910044a8a942cdd298dd88f3
Source dataset
uspto-grants-2013_10
Patent number
US08569300B2

Reaction notes

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