1,2-Dichloroethane → (4-Isopropyl-piperazin-1-yl)-(5-piperidin-1-ylmethylpyrazin-2-yl)-methanone

HRID 30482Notes

Reaction equation

HRID 30482 reaction equation
[N:1]1([CH2:7][C:8]2[N:9]=[CH:10][C:11]([C:14]([OH:16])=O)=[N:12][CH:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.Cl.[CH:19]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)([CH3:21])[CH3:20].C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.C(Cl)CCl>C(Cl)Cl>[CH:19]([N:22]1[CH2:27][CH2:26][N:25]([C:14]([C:11]2[CH:10]=[N:9][C:8]([CH2:7][N:1]3[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]3)=[CH:13][N:12]=2)=[O:16])[CH2:24][CH2:23]1)([CH3:21])[CH3:20]

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 122683781-Isopropylpiperazine dihydrochlorideHCID 67189685HCID 67189685, compound

Product 1

HCID 11544498(4-Isopropyl-piperazin-1-yl)-(5-piperidin-1-ylmethylpyrazin-2-yl)-methanoneYield 28.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-piperidin-1-ylmethyl-pyrazine-2-carboxylic acid (0.125 g, 0.53 mmol),1-isopropyl-piperazine dihydrochloride (0.117 g, 0.58 mmol), HOBt (0.086 g, 0.64 mmol) and N-methylmorpholine (0.323 g, 3.19 mmol) in DCM (7 mL) was stirred for 1 h. The mixture was then treated with EDC (0.122 g, 0.64 mmol) and stirring was continued for 18 h. The reaction was quenched by the addition of 1 N NaOH (10 mL), and was stirred for 30 min. The mixture was diluted with H2O (10 mL) and extracted with DCM (3×15 mL). The combined organic layers were dried over Na2SO4, filtered, and concentrated to yield the crude product (0.145 g). The crude was purified on SiO2 using 0-5% 2 M NH3 in MeOH/DCM to provide the title compound (0.05 g, 26%). MS (ESI): exact mass calcd. for C18H29N5O, 331.46; m/z found 332.5 [M+H]+. 1HNMR (500 MHz, CDCl3): 8.85 (d, J=1.4,1H), 8.64 (d, J=1.4, 1H), 3.82 (t, J=4.9, 2H), 3.68 (s, 2H), 3.63 (t, J=4.9, 2H), 2.77-2.70 (m, 1H), 2.62 (t, J=4.9, 2H), 2.53 (t, J=4.9, 2H), 2.48-2.42 (m, 4H), 1.63-1.57 (m, 4H), 1.49-1.42 (m, 2H), 1.05 (d, J=6.6, 6H).

Workup

  1. stirringstirring
  2. waitwas continued for 18 h
  3. customThe reaction was quenched by the addition of 1 N NaOH (10 mL)
  4. stirringwas stirred for 30 min
  5. additionThe mixture was diluted with H2O (10 mL)
  6. extractionextracted with DCM (3×15 mL)
  7. dry with materialThe combined organic layers were dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto yield the crude product (0.145 g)
  11. customThe crude was purified on SiO2 using 0-5% 2 M NH3 in MeOH/DCM

Sources & evidence

ORD record
ord-3db0d58a6bd34c189024e1aa224bad08
Source dataset
uspto-grants-2008_09
Patent number
US07423147B2

Reaction notes

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