Dimethylformamide → Tert-butyl 4-(3-chloropyrazin-2-yl)-3-methylpiperazine-1-carboxylate

HRID 907532

Reaction equation

HRID 907532 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH:10]([CH3:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:15][C:16]1[C:21](Cl)=[N:20][CH:19]=[CH:18][N:17]=1.CN(C=O)C>O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:21]2[C:16]([Cl:15])=[N:17][CH:18]=[CH:19][N:20]=2)[CH:10]([CH3:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 785752,3-DichloropyrazineHCID 2756810tert-Butyl 3-methylpiperazine-1-carboxylate

Product 1

HCID 21908991Tert-butyl 4-(3-chloropyrazin-2-yl)-3-methylpiperazine-1-carboxylateYield 45%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

3-Methyl-piperazine-1-carboxylic acid tert-butyl ester (5.0 g, 25 mmol), 2,3-dichloropyrazine (1.3 mL, 12.5 mmol), and DMF (5.0 mL) were combined and heated to 100 C overnight with stirring. The reaction mixture was poured into H2O and extracted with EtOAc (3×). The combined EtOAc extractions were washed with sat'd NaHCO3 (2×), sat's NaCl (1×), dried (Na2SO4), and concentrated in vacuo. The crude product was purified by column chromatography (4:1 hexanes:EtOAc) to give 1.76 g (45%) of 3′-chloro-2-methyl-2,3,5,6-tetrahydro-[1,2′]bipyrazinyl-4-carboxylic acid tert-butyl ester. 1H NMR (CDCl3) 8.08 (d, 1H), 7.86 (d, 1H), 4.22-3.76 (complex m, 3H), 3.48-3.17 (complex m, 4H), 1.48 (s, 9H), 1.19 (d, 3H) ppm. LC-MS (MH+)=257 (-t-butyl).

Workup

  1. temperatureheated to 100 C overnight
  2. extractionextracted with EtOAc (3×)
  3. extractionThe combined EtOAc extractions
  4. washwere washed with sat'd NaHCO3 (2×), sat's NaCl (1×)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. customThe crude product was purified by column chromatography (4:1 hexanes:EtOAc)

Sources & evidence

ORD record
ord-8ac4cfe6e9454662b3402a2c0b3b48f0
Source dataset
uspto-grants-2011_09
Patent number
US08013156B2

Linked notes

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