Acetamidine → 12-chloro-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetra-deca1(14),2,4,10,12-pentaene

HRID 1530638Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1530638
[Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][N:15]=1)[C:12]1[N:8]([CH:9]=[C:10](I)[N:11]=1)[CH2:7][CH2:6][O:5]2.[C:17](=[NH:20])([NH2:19])[CH3:18].[CH3:21][C:22]1([CH3:62])C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.COC(C)[CH2:66][NH:67]N>CN(C=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].C(O)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]2[C:13](=[CH:14][N:15]=1)[C:12]1[N:8]([CH:9]=[C:10]([C:66]3[N:67]([CH:22]([CH3:62])[CH3:21])[N:19]=[C:17]([CH3:18])[N:20]=3)[N:11]=1)[CH2:7][CH2:6][O:5]2

Komponenten

8

Edukt 4

HCID 67171AcetamidineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 582047809-Chloro-2-iodo-5,6-dihydroimidazo[1,2-d]pyrido[3,4-f][1,4]oxazepineHCID 86671471(2-Methoxypropyl)hydrazine

Produkt 1

HCID 8893255312-chloro-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetra-deca1(14),2,4,10,12-pentaeneAusbeute 338,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 176Acetic AcidLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
40 °C

Versuchsvorschrift

To a solution of 12-chloro-4-iodo-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene (2.0 g, 5.8 mmol) in dry DMF (20 mL) was added hydrochloric acetimidamide (595 mg, 6.30 mmol), Pd(OAc)2 (130 mg, 0.580 mmol), and Xantphos (695 mg, 1.2 mmol). The mixture was stirred at 40° C. for 3 h under carbon monoxide atmosphere. LCMS indicated complete conversion. Acetic acid (40 mL) and hydrochloric (2-methoxypropyl)hydrazine (1.3 g, 12 mmol) were added. The resultant mixture was stirred at 100° C. for 1 h. After concentration, the residue was purified by silica gel chromatography eluting with DCM/methanol (100:1) to give 12-chloro-4-[3-methyl-1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetra-deca1(14),2,4,10,12-pentaene (1.4 g, 71% yield) as a white solid. LCMS (ESI) m/z: 345.3 [M+H+].

Aufarbeitung

  1. concentrationAfter concentration
  2. customthe residue was purified by silica gel chromatography
  3. washeluting with DCM/methanol (100:1)

Quellen und Nachweise

ORD-Eintrag
ord-e965352863c84ee1af302f1cca37ae5e
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09090628B2

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