Triethylamine → HCID 53677056, compound

HRID 1432937Notes

Reaction equation

HRID 1432937 reaction equation
[NH2:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][C:5]1=[O:17].Cl[C:19]1[N:20]=[N:21][CH:22]=[C:23](Cl)[C:24]=1Cl.C(N(CC)CC)C.[H][H]>C(OCC)(=O)C.C[O-].[Na+].CO.[Pd].C1COCC1>[C:13]([O:12][C:10]([N:7]1[CH2:8][CH2:9][N:4]([CH2:3][CH2:2][NH:1][C:24]2[CH:23]=[CH:22][N:21]=[N:20][CH:19]=2)[C:5](=[O:17])[CH2:6]1)=[O:11])([CH3:14])([CH3:16])[CH3:15]

Participants

10

Reactant 4

HCID 8471TriethylamineHCID 701113,4,5-TrichloropyridazineHCID 54065570HCID 54065570, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 53677056HCID 53677056, compound

Reagents, catalysts & solvents 5

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 10942334Sodium MethoxideSolvent

Conditions

Temperature
120 °C

Procedure

1-(2-Aminoethyl)-4-(tert-butyloxycarbonyl)-piperazin-2-one from EXAMPLE 92, Part A (1.0 g, 4.1 mmol) is treated with 3,4,5-trichloropyridazine (0.81 g, 4.1 mmol), triethylamine (0.57 mL, 4.1 mmol), THF (25 mL) and heated to 120° C. in a sealed tube for 3 hours. Upon cooling, the solution is diluted with ethyl acetate and washed with aqueous sodium bicarbonate (25 mL), water and dried over sodium sulfate. The organic layer is concentrated and chromatographed (5% methanol/methylene chloride) to give a mixture of isomers (0.8 g, 20 mmol). The mixture is dissolved in 0.5 M sodium methoxide in methanol (200 mL), treated with 10% Pd/C (0.5 g) and agitated under 50 PSI of hydrogen for 20 hours. The reaction mixture is filtered; the filtrate is concentrated to a residue which is chromatographed (NH4OH/H2O/MeOH/EtOAc, 1:1:2:90) to give crude 4-(tert-butyloxycarbonyl)-1-[2-(pyridazin-4-ylamino)-ethyl]-piperazin-2-one. This material is dissolved in a minimal amount of THF and treated with a saturated solution of HCl in ethyl acetate (50 mL). The solution is stirred at ambient temperature for 2 h and diluted with diethyl ether (50 mL). The precipitated title compound is collected and air dried (0.5 g, 1.7 mmol). MS m/z: 367, [M+1]+; 1H NMR (CD3OD, 300 MHz) δ8.8 (d, 1H), 8.5 (s, 1H), 7.4 (d, 1H), 4.1 (s, 2H), 3.5-3.8 (m, 8H).

Workup

  1. temperatureUpon cooling
  2. washwashed with aqueous sodium bicarbonate (25 mL), water
  3. dry with materialdried over sodium sulfate
  4. concentrationThe organic layer is concentrated
  5. customchromatographed (5% methanol/methylene chloride)
  6. customto give
  7. additiona mixture of isomers (0.8 g, 20 mmol)
  8. filtrationThe reaction mixture is filtered
  9. concentrationthe filtrate is concentrated to a residue which
  10. customis chromatographed (NH4OH/H2O/MeOH/EtOAc, 1:1:2:90)

Sources & evidence

ORD record
ord-4085854e87df43d083aa30a8c68c11d8
Source dataset
uspto-grants-2009_11
Patent number
US07612075B2

Reaction notes

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