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 570606Notes

Reaction equation

HRID 570606 reaction equation
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

Participants

7

Reactant 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

Product 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

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-85d11489dc94462da7e72f97fb9ed41a
Source dataset
uspto-grants-2015_05
Patent number
US09023851B2

Reaction notes

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