1,2-Dichloroethane → HCID 58229894, Verbindung

HRID 221978

Reaktionsgleichung

Reaktionsgleichung von HRID 221978
[CH3:1][N:2]1[CH:6]=[C:5]([C:7](O)=O)[N:4]=[CH:3]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH:24]([C:26]1[N:35]=[CH:34][CH:33]=[C:32]2[C:27]=1[CH:28]=[C:29]([C:58]1[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=1)[C:30]([C:36]1[CH:41]=[CH:40][C:39]([C:42]3([NH:50][C:51](=[O:57])[O:52][C:53]([CH3:56])([CH3:55])[CH3:54])[CH2:45][C:44]4([O:49][CH2:48][CH2:47][O:46]4)[CH2:43]3)=[CH:38][CH:37]=1)=[N:31]2)[NH2:25].C(O)(=O)C>CC(N(C)C)=O>[CH3:1][N:2]1[CH:6]=[C:5]([C:7]2[N:35]3[C:26]([C:27]4[CH:28]=[C:29]([C:58]5[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=5)[C:30]([C:36]5[CH:41]=[CH:40][C:39]([C:42]6([NH:50][C:51](=[O:57])[O:52][C:53]([CH3:56])([CH3:55])[CH3:54])[CH2:45][C:44]7([O:49][CH2:48][CH2:47][O:46]7)[CH2:43]6)=[CH:38][CH:37]=5)=[N:31][C:32]=4[CH:33]=[CH:34]3)=[N:24][N:25]=2)[N:4]=[CH:3]1

Komponenten

7

Edukt 5

HCID 111,2-DichloroethaneHCID 176Acetic AcidHCID 757711-HydroxybenzotriazoleHCID 5415091-methyl-1H-imidazole-4-carboxylic acidHCID 58229864HCID 58229864, Verbindung

Produkt 1

HCID 58229894HCID 58229894, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Versuchsvorschrift

To a solution of 1-methyl-1H-imidazole-4-carboxylic acid (7.0 g, 56 mmol) in DMA (200 mL) was added EDC (11 g, 56 mmol) and HOBt (8.5 g, 56 mmol) and the reaction mixture was stirred at room temperature for 1 hour. Then tert-butyl {2-[4-(5-hydrazino-3-phenyl-1,6-naphthyridin-2-yl)phenyl]-5,8-dioxaspiro[3.4]oct-2-yl}carbamate (1-10) (30 g, 56 mmol) was added and the reaction stirred at room temperature for an additional 1 hour at which time acetic acid (17 g, 280 mmol) was added and the reaction was stirred overnight at 80° C., The reaction mixture was cooled to room temperature, quenched with 1N NaOH, poured into saturated sodium bicarbonate, extracted with EtOAc, dried (Na2SO4), filtered and concentrated. The crude residue was purified by column chromatography eluting with 10% methanol in DCM. The appropriate fractions were concentrated and the resulting solid was recrystallized from methanol to give tert-butyl (2-{4-[3-(1-methyl-1H-imidazol-4-yl)-9-phenyl[1,2,4]triazolo[3,4-f]-1,6-naphthyridin-8-yl]phenyl}-5,8-dioxaspiro[3.4]oct-2-yl)carbamate (1-11) as a white solid. MS (M+H)+: 630.

Aufarbeitung

  1. additionwas added
  2. stirringthe reaction was stirred overnight at 80° C.
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customquenched with 1N NaOH
  5. additionpoured into saturated sodium bicarbonate
  6. extractionextracted with EtOAc
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude residue was purified by column chromatography
  11. washeluting with 10% methanol in DCM
  12. concentrationThe appropriate fractions were concentrated
  13. customthe resulting solid was recrystallized from methanol

Quellen und Nachweise

ORD-Eintrag
ord-b7cc9e988695408ead0fce38b95d045a
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08207169B2

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