1,4-Dioxane → N8-{3-Chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl}-N2-(3,5-dimethyl-phenylamino) [1,2,4]triazolo[1,5-a]pyrazine-2,8-diamine

HRID 570606Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 570606
Cl[C:2]1[C:3]2[N:4]([N:8]=[C:9]([NH:11]C3C=C(C)C=C(C)C=3)[N:10]=2)[CH:5]=[CH:6][N:7]=1.C1(P(C2CCCCC2)[C:27]2C=CC=[CH:29][C:28]=2[C:33]2C=CC=[CH:35][C:34]=2[N:39](C)C)CCCCC1.[Cl:48][C:49]1[CH:50]=[C:51]([CH:53]=[CH:54][C:55]=1[S:56][C:57]1[N:58]([CH3:62])[CH:59]=[CH:60][N:61]=1)[NH2:52].O1[CH2:68][CH2:67]OCC1>O1CCCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:48][C:49]1[CH:50]=[C:51]([NH:52][C:2]2[C:3]3[N:4]([N:8]=[C:9]([NH:11][NH:39][C:34]4[CH:33]=[C:28]([CH3:29])[CH:27]=[C:67]([CH3:68])[CH:35]=4)[N:10]=3)[CH:5]=[CH:6][N:7]=2)[CH:53]=[CH:54][C:55]=1[S:56][C:57]1[N:58]([CH3:62])[CH:59]=[CH:60][N:61]=1

Komponenten

7

Edukt 4

HCID 312751,4-DioxaneHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 114590883-chloro-4-(1-methyl-1H-imidazol-2-ylsulfanyl)phenylamineHCID 866943458-Chloro-[1,2,4]triazolo[1,5-a]pyrazin-2-yl-(3,5-dimethyl-phenyl)-amine

Produkt 1

HCID 86694344N8-{3-Chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]phenyl}-N2-(3,5-dimethyl-phenylamino) [1,2,4]triazolo[1,5-a]pyrazine-2,8-diamine

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

8-Chloro-[1,2,4]triazolo[1,5-a]pyrazin-2-yl-(3,5-dimethyl-phenyl)-amine (0.1 g, 0.3 mmol), tris(dibenzylideneacetone)dipalladium(0) (14.0 mg, 0.01 mmol), 2-dicyclohexylphosphino-2′-(N,N-dimethylamino)biphenyl (14.4 mg, 0.03 mmol) and 3-chloro-4-[(1-methyl-1H-imidazol-2-yl)thio]aniline (96.6 mg, 0.4 mmol) are taken in dry 1,4 dioxane (3 mL). Lithiumhexamethyldiisilylamide (1 M in tetrahydrofuran) (0.15 mL, 0.1 mmol) is added and the reaction mixture irradiated in the microwave at 150° C. for 45 minutes. The reaction mixture is then quenched with dry methanol (1 mL) and passed through a celite pad. The filtrate is concentrated and purified by flash column chromatography column using silica gel (230-400) mesh to get the titled product as an off white solid (27 mg, 10.4%); TLC: pet ether/ethylacetate (6/4) Rf-0.4. LCMS (method A): mass found (M+H+, 477.0), Rt (min): 4.39 area % 90.1 (max), 91.0 (254 nm); 1H NMR (400 MHz, DMSO-d6): δ [ppm] 9.69 (s, 1H), 9.38 (s, 1H), 8.30 (t, J=4.76 Hz, 2H), 7.79 (m, 1H), 7.61 (d, J=4.48 Hz, 1H), 7.50 (m, 1H), 7.33 (s, 2H), 7.12 (m, 1H), 6.61 (m, 1H), 6.54 (s, 1H), 3.63 (s, 3H), 2.49 (s, 6H).

Aufarbeitung

  1. customthe reaction mixture irradiated in the microwave at 150° C. for 45 minutes
  2. customThe reaction mixture is then quenched with dry methanol (1 mL)
  3. concentrationThe filtrate is concentrated
  4. custompurified by flash column chromatography column

Quellen und Nachweise

ORD-Eintrag
ord-85d11489dc94462da7e72f97fb9ed41a
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09023851B2

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