Trichloroacetyl chloride → 4-(Tetrahydro-pyran-4-carbonyl)-[1,4]diazepane-1-carboxylic acid (5-sec-butyl-pyridin-2-yl)-amide

HRID 1920729Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1920729
[CH:1]([C:5]1[CH:6]=[CH:7][C:8]([NH2:11])=[N:9][CH:10]=1)([CH2:3][CH3:4])[CH3:2].C(N(CC)C(C)C)(C)C.ClC(Cl)(Cl)[C:23](Cl)=[O:24].C([O-])(O)=O.[Na+].[N:33]1([C:40]([CH:42]2[CH2:47][CH2:46][O:45][CH2:44][CH2:43]2)=[O:41])[CH2:39][CH2:38][CH2:37][NH:36][CH2:35][CH2:34]1.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl>[CH:1]([C:5]1[CH:6]=[CH:7][C:8]([NH:11][C:23]([N:36]2[CH2:37][CH2:38][CH2:39][N:33]([C:40]([CH:42]3[CH2:47][CH2:46][O:45][CH2:44][CH2:43]3)=[O:41])[CH2:34][CH2:35]2)=[O:24])=[N:9][CH:10]=1)([CH2:3][CH3:4])[CH3:2]

Komponenten

8

Edukt 6

HCID 6420Trichloroacetyl chlorideHCID 10340Sodium CarbonateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 206746695-Sec-butyl-pyridin-2-ylamineHCID 28776660(1,4-Diazepan-1-yl)(tetrahydro-2H-pyran-4-yl)methanone

Produkt 1

HCID 591433804-(Tetrahydro-pyran-4-carbonyl)-[1,4]diazepane-1-carboxylic acid (5-sec-butyl-pyridin-2-yl)-amideAusbeute 9 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of 90 mg (0.6 mmol) of 5-sec-butyl-pyridin-2-ylamine in DCM (2 mL) was added N,N-diisopropylethylamine (348 μL, 1.2 mmol), followed by 67 μL (0.6 mmol) of trichloroacetylchloride. The reaction mixture was shaken on an orbital shaker for 18 h. Saturated aqueous NaHCO3 solution (3 mL) was added to the reaction mixture. The organic layer was dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. The residue was dissolved in DMF (2 mL) and added to 332 mg (0.6 mmol) of [1,4]diazepan-1-yl-(tetrahydro-pyran-4-yl)-methanone (triple trifluoroacetic acid salt). To this solution 254 mg (2.4 mmol) of Na2CO3 were added and the mixture was heated in a sealed tube at 100° C. for 18 h. The reaction was cooled to room temperature, filtered and the filtrate was concentrated under reduced pressure. The residue was purified by mass-triggered preparative LC-MS to afford 21 mg of 4-(tetrahydro-pyran-4-carbonyl)-[1,4]diazepane-1-carboxylic acid (5-sec-butyl-pyridin-2-yl)-amide. ES−MS: m/z 389;

Aufarbeitung

  1. dry with materialThe organic layer was dried over Na2SO4
  2. filtrationfiltered
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. dissolutionThe residue was dissolved in DMF (2 mL)
  5. temperatureThe reaction was cooled to room temperature
  6. filtrationfiltered
  7. concentrationthe filtrate was concentrated under reduced pressure
  8. customThe residue was purified by mass-triggered preparative LC-MS

Quellen und Nachweise

ORD-Eintrag
ord-5c04c501a01846e58284b4dd33d0f5fc
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08173638B2

Notizen zur Reaktion

Wird geladen…