1-[5-(Trifluoromethyl)pyridin-2-yl]-1,4-diazepane → HCID 178518719, Verbindung

HRID 1923483Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1923483
[O:1]=[C:2]1[NH:7][C:6](=[O:8])[C:5]2[CH:9]=[C:10]([C:13]3[C:17]([CH:18]=O)=[CH:16][NH:15][N:14]=3)[CH:11]=[CH:12][C:4]=2[O:3]1.[F:20][C:21]([F:36])([F:35])[C:22]1[CH:23]=[CH:24][C:25]([N:28]2[CH2:34][CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)=[N:26][CH:27]=1>C(Cl)Cl.CO.C(O)(=O)C>[F:36][C:21]([F:20])([F:35])[C:22]1[CH:23]=[CH:24][C:25]([N:28]2[CH2:34][CH2:33][CH2:32][N:31]([CH2:18][C:17]3[C:13]([C:10]4[CH:11]=[CH:12][C:4]5[O:3][C:2](=[O:1])[NH:7][C:6](=[O:8])[C:5]=5[CH:9]=4)=[N:14][NH:15][CH:16]=3)[CH2:30][CH2:29]2)=[N:26][CH:27]=1

Komponenten

6

Edukt 2

HCID 27607791-[5-(Trifluoromethyl)pyridin-2-yl]-1,4-diazepaneHCID 178519872HCID 178519872, Verbindung

Produkt 1

HCID 178518719HCID 178518719, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 176Acetic AcidLösungsmittelHCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

The mixture of 3-(2,4-dioxo-3,4-dihydro-2H-benzo[e][1,3]oxazin-6-yl)-1H-pyrazole-4-carbaldehyde (51.4 mg, 0.2 mmol) and 1-(5-trifluoromethyl-pyridin-2-yl)-[1,4]diazepane (24.5 mg, 0.1 mmol) in methylene chloride (1.0 mL), methanol (0.5 mL) and acetic acid (15 μL) is stirred for 30 minutes at room temperature. Then Na(AcO)3BH (84 mg, 4.0 equiv.) is added and the reaction is stirred overnight at room temperature. After evaporation, the residue is redissolved in DMF (1.0 mL) which is subject to reverse-phase preparative LC-MS (acetonitrile/water/TFA gradient 10-90% CH3CN in 7.5 min, Ultro 120 5 uM C18Q, 75×30 mmID) The collected water/MeCN solution of the TFA salt of the product is evaporated to remove the acetonitrile. A saturated aqueous solution of NaHCO3 is added to raise the pH to about 8-9. Then ethyl acetate is used to extract the product and the organic phase is dried with Na2SO4. Evaporation of the solvent yields the free-based 6-{4-[4-(5-trifluoromethyl-pyridin-2-yl)-[1,4]diazepan-1-ylmethyl]-1H-pyrazol-3-yl}-benzo[e][1,3]oxazine-2,4-dione.

Aufarbeitung

  1. stirringthe reaction is stirred overnight at room temperature
  2. customAfter evaporation
  3. dissolutionthe residue is redissolved in DMF (1.0 mL) which
  4. customis subject to reverse-phase preparative LC-MS (acetonitrile/water/TFA gradient 10-90% CH3CN in 7.5 min, Ultro 120 5 uM C18Q, 75×30 mmID)
  5. customis evaporated
  6. customto remove the acetonitrile
  7. additionA saturated aqueous solution of NaHCO3 is added
  8. temperatureto raise the pH to about 8-9
  9. extractionto extract the product
  10. dry with materialthe organic phase is dried with Na2SO4
  11. customEvaporation of the solvent

Quellen und Nachweise

ORD-Eintrag
ord-825bc07b4b9640dc958ecb5a8c201587
Quelldatensatz
uspto-grants-2012_05
Patentnummer
US08178526B2

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