Diisopropylethylamine → HCID 86635174, compound

HRID 219730

Reaction equation

HRID 219730 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([C:7]([OH:9])=O)=[CH:3][N:2]=1.[C:10]([C:14]1[N:19]=[C:18]([N:20]2[CH2:25][CH2:24][N:23]([CH2:26][CH2:27][CH2:28][CH2:29][NH2:30])[CH2:22][CH2:21]2)[CH:17]=[C:16]([CH:31]2[CH2:34][CH2:33][CH2:32]2)[N:15]=1)([CH3:13])([CH3:12])[CH3:11].C(N(C(C)C)CC)(C)C.OC1C2N=NNC=2C=CC=1.[ClH:54].C(N=C=NCCCN(C)C)C>ClCCl>[ClH:54].[ClH:54].[C:10]([C:14]1[N:19]=[C:18]([N:20]2[CH2:21][CH2:22][N:23]([CH2:26][CH2:27][CH2:28][CH2:29][NH:30][C:7]([C:4]3[CH:5]=[CH:6][N:1]=[N:2][CH:3]=3)=[O:9])[CH2:24][CH2:25]2)[CH:17]=[C:16]([CH:31]2[CH2:34][CH2:33][CH2:32]2)[N:15]=1)([CH3:13])([CH3:11])[CH3:12]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 2761046Pyridazine-4-carboxylic AcidHCID 690260674-[4-(2-tert-Butyl-6-cyclobutyl-pyrimidin-4-yl)piperazin-1-yl]-butylamineHCID 178418300HCID 178418300, compound2×

Product 2

HCID 313Hydrochloric AcidHCID 86635174HCID 86635174, compoundYield 117.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

0.25 g of 4-pyridazine-carboxylic acid (2.01 mmol) and 0.7 g of 4-[4-(2-tert-butyl-6-cyclobutyl-pyrimidin-4-yl)-piperazin-1-yl]-butylamine (2.01 mmol) were dissolved in 25 ml of dichloromethane. 1.04 g of diisopropylethylamine (8.04 mmol), 0.19 g of hydroxybenzotriazole (HOBt, 1.4 mmol), and 0.46 g of N-ethyl-N′-(3-dimethylaminopropyl)-carbodiimide hydrochloride (EDCl, 2.4 mmol) were added at 0° C. and the reaction mixture was stirred for 16 h at room temperature. 0.09 g of hydroxybenzotriazole and 0.23 g of N-ethyl-N′-(3-dimethylaminopropyl)-carbodiimide hydrochloride were added and the reaction mixture was stirred 5 h. 25 ml of dichloromethane were added, the organic layer was washed with aqueous saturated sodium chloride, the aqueous phase re-extracted once with dichloromethane. The combined organic phases were dried over magnesium sulfate, filtered, and concentrated to dryness. The crude product was purified by chromatography on silica gel using ethyl acetate and ethyl acetate-methanol (10%). Fractions containing the product were combined, the solvent evaporated, and the residue re-dissolved in 20 ml of ethyl acetate. Treatment with 3.3 ml of 1 N hydrochloride acid in diethyl ether yielded 0.69 g of the title compound as a white solid.

Workup

  1. stirringthe reaction mixture was stirred 5 h
  2. washthe organic layer was washed with aqueous saturated sodium chloride
  3. extractionthe aqueous phase re-extracted once with dichloromethane
  4. dry with materialThe combined organic phases were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe crude product was purified by chromatography on silica gel
  8. additionFractions containing the product
  9. customthe solvent evaporated
  10. dissolutionthe residue re-dissolved in 20 ml of ethyl acetate

Sources & evidence

ORD record
ord-bbd585d3cdc0431781d960ac945f80e4
Source dataset
uspto-grants-2012_06
Patent number
US08202868B2

Linked notes

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