1,2-Dimethoxyethane → 8-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene

HRID 886194Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 886194
[Br:1][C:2]1[CH:18]=[CH:17][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]([NH2:16])=O)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1.[CH3:19]OC(OC)N(C)C.COCCOC.Cl.[CH:34]([NH:37][NH2:38])([CH3:36])[CH3:35]>C(O)(=O)C>[Br:1][C:2]1[CH:18]=[CH:17][C:5]2[C:6]3[N:7]([CH:11]=[C:12]([C:14]4[N:37]([CH:34]([CH3:36])[CH3:35])[N:38]=[CH:19][N:16]=4)[N:13]=3)[CH2:8][CH2:9][O:10][C:4]=2[CH:3]=1

Komponenten

6

Edukt 4

HCID 80711,2-DimethoxyethaneHCID 78373Dimethylformamide dimethyl acetalHCID 855731-Isopropylhydrazine hydrochlorideHCID 582046299-Bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide

Produkt 1

HCID 582043138-bromo-2-(2-isopropyl-2H-[1,2,4]triazol-3-yl)-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azuleneAusbeute 39 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 176Acetic AcidLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

9-Bromo-5,6-dihydrobenzo[f]imidazo[1,2-d][1,4]oxazepine-2-carboxamide (4.93 g, 16.0 mmol) was taken up in 1,1-dimethoxy-N,N-dimethylmethanamine (25 mL, 0.18 mol) and 1,2-dimethoxyethane (66.5 mL, 0.640 mol). The heterogeneous mixture was stirred very vigorously and heated at 65° C. for 1 h. LC/MS showed complete consumption of starting material at the end of this period. The reaction mixture was concentrated in vacuo and carried on to the subsequent reaction with no further purification steps applied. The crude product from the previous reaction (5.8 g, 16.0 mmol) was suspended in glacial acetic acid (53.2 mL) and isopropylhydrazine hydrochloride (4.36 g, 39.4 mmol) was added. The mixture was heated at 100° C. for 2 h. The reaction vessel was cooled to room temp and the solvent was removed in vacuo. The resultant residue was dry loaded onto silica gel and purified by ISCO chromatography (120 g column, 100% EtOAc). In total, 2.3 g (39% yield) of 194 was isolated over the two steps. LC/MS (ESI+): m/z 376 (M+H, with halide isotope). 1H NMR (400 MHz, DMSO) δ 8.34 (d, J=8.6, 1H), 7.95 (s, 1H), 7.91 (s, 1H), 7.36 (dd, J=8.7, 2.0, 1H), 7.30 (d, J=2.0, 1H), 5.85 (dt, J=13.3, 6.6, 1H), 4.55 (d, J=15.5, 4H), 1.48 (d, J=6.6, 6H)

Aufarbeitung

  1. customconsumption of starting material at the end of this period
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customcarried on to the subsequent reaction with no further purification steps
  4. temperatureThe mixture was heated at 100° C. for 2 h
  5. temperatureThe reaction vessel was cooled to room temp
  6. customthe solvent was removed in vacuo
  7. dry with materialThe resultant residue was dry
  8. custompurified by ISCO chromatography (120 g column, 100% EtOAc)

Quellen und Nachweise

ORD-Eintrag
ord-63c3a8b75a3f4aa694f5e4f6d71da29d
Quelldatensatz
uspto-grants-2012_08
Patentnummer
US08242104B2

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