1,2-Dichloroethane → HCID 69642023, Verbindung

HRID 1611100Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1611100
Cl.C(Cl)CCl.[CH3:6][O:7][C:8]1[CH:9]=[C:10]([C:16]2[CH:17]=[N:18][C:19]([CH2:22][CH2:23][C:24]([OH:26])=O)=[N:20][CH:21]=2)[CH:11]=[CH:12][C:13]=1[O:14][CH3:15].[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][CH2:37][CH:36]([CH2:40][NH2:41])[CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28].C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>>[C:27]([O:31][C:32]([N:34]1[CH2:39][CH2:38][CH2:37][CH:36]([CH2:40][NH:41][C:24](=[O:26])[CH2:23][CH2:22][C:19]2[N:20]=[CH:21][C:16]([C:10]3[CH:11]=[CH:12][C:13]([O:14][CH3:15])=[C:8]([O:7][CH3:6])[CH:9]=3)=[CH:17][N:18]=2)[CH2:35]1)=[O:33])([CH3:30])([CH3:29])[CH3:28]

Komponenten

7

Edukt 6

HCID 111,2-DichloroethaneHCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27564831-Boc-3-(aminomethyl)piperidineHCID 222579115-(3,4-Dimethoxyphenyl)-2-pyrimidinepropanoic acid

Produkt 1

HCID 69642023HCID 69642023, VerbindungAusbeute 84 %

Versuchsvorschrift

The mono HCl salt of EDC (0.86 g, 4.5 mmol, 1.5 equiv) was added to a suspension of 3-(5-(3,4-dimethoxy-phenyl)pyrimidin-2-yl)-propanoic acid (0.95 g, 3.3 mmol, 1.1 equiv), 3-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester (0.64 g, 3.0 mmol), HOBT (0.61 g, 4.5 mmol, 1.5 equiv), and diisopropylethylamine (1.3 mL, 7. mmol, 2.5 equiv) in a 50 mL solvent (THF:DMF, 7:3). After stirring overnight at rt, the mixture was concentrated and the residue was dissolved in 50 mL ethyl acetate. The solution was poured into 50 mL of a saturated NaHCO3 solution and extracted thoroughly with ethyl acetate. The combined organic layers were washed with brine and water, dried (Na2SO4), and concentrated. The residue was purified by flash chromatography (0→10% MeOH in CHCl3). Clean fractions containing the desired product were combined and concentrated to give 3-({3-[5-(3,4-dimethoxy-phenyl)-pyrimidin-2-yl]-propionylamino}-methyl)-piperidine-1-carboxylic acid tert-butyl ester (1.22 g, 84%) as a dark brown solid. The solid was dissolved into CH2Cl2 (30 mL) and neat TFA (5 mL) added dropwise. After about 30 min, the solution was concentrated to an oil on the teflon dryvac, then under high vacuum. LCMS analysis indicated quantitative conversion to 3-[5-(3,4-dimethoxy-phenyl)-pyrimidin-2-yl]-N-piperidin-3-ylmethyl-propionamide 2c.

Aufarbeitung

  1. concentrationthe mixture was concentrated
  2. dissolutionthe residue was dissolved in 50 mL ethyl acetate
  3. additionThe solution was poured into 50 mL of a saturated NaHCO3 solution
  4. extractionextracted thoroughly with ethyl acetate
  5. washThe combined organic layers were washed with brine and water
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography (0→10% MeOH in CHCl3)
  9. additionClean fractions containing the desired product
  10. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-e0eaf2cce6b04058ba16466f73e3d748
Quelldatensatz
uspto-grants-2006_01
Patentnummer
US06984643B2

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