Methyl 5-chloropyrazine-2-carboxylate → Methyl 5-(4-(6-benzyl-4,5-dimethylpyridazin-3-yl)-5,6-dihydropyridin-1(2H)-yl)pyrazine-2-carboxylate

HRID 1479953Notes

Reaction equation

HRID 1479953 reaction equation
[CH2:1]([C:8]1[N:9]=[N:10][C:11]([C:16]2[CH2:17][CH2:18][NH:19][CH2:20][CH:21]=2)=[C:12]([CH3:15])[C:13]=1[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:22][O:23][C:24]([C:26]1[CH:31]=[N:30][C:29](Cl)=[CH:28][N:27]=1)=[O:25]>O1CCOCC1>[CH2:1]([C:8]1[N:9]=[N:10][C:11]([C:16]2[CH2:17][CH2:18][N:19]([C:29]3[N:30]=[CH:31][C:26]([C:24]([O:23][CH3:22])=[O:25])=[N:27][CH:28]=3)[CH2:20][CH:21]=2)=[C:12]([CH3:15])[C:13]=1[CH3:14])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 406081Methyl 5-chloropyrazine-2-carboxylateHCID 671797893-Benzyl-4,5-dimethyl-6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazine

Product 1

HCID 59191506Methyl 5-(4-(6-benzyl-4,5-dimethylpyridazin-3-yl)-5,6-dihydropyridin-1(2H)-yl)pyrazine-2-carboxylateYield 30%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
160 °C

Procedure

To 4-(6-benzyl-4,5-dimethyl-pyridazin-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (170 mg, 0.358 mmol) is added 50% TFA in DCM. The reaction mixture is stirred for 10 min and concentrated to afford 3-benzyl-4,5-dimethyl-6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazine as a yellow sticky solid (125 mg, 100%). To a solution of 3-benzyl-4,5-dimethyl-6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazine (180 mg, 0.644 mmol) in dioxane is added methyl-5-chloropyrazine-2-carboxylate (222 mg, 1.29 mmol) and TEA (0.45 mL, 3.22 mmol) in a microwave tube. The reaction mixture is heated at 160° C. for 40 min in a microwave reactor. The mixture is concentrated to afford a brown oil and purified by prep HPLC, eluting with 10%-100% acetonitrile:water (both mobile phases modified by 3% n-PrOH). Fractions containing the desired product are combined and freeze-dried to afford a white solid (80 mg, 30%).

Workup

  1. concentrationThe mixture is concentrated
  2. customto afford a brown oil
  3. custompurified by prep HPLC
  4. washeluting with 10%-100% acetonitrile
  5. additionFractions containing the desired product
  6. customfreeze-dried

Sources & evidence

ORD record
ord-b7b1a4dc7f2946f6850c3ddc0852b27a
Source dataset
uspto-grants-2016_08
Patent number
US09409871B2

Reaction notes

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