Water → N-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-2-methyl-1,3-thiazole-4-carboxamide

HRID 244725Notes

Reaction equation

C(=O)([O-])[O-].[Na+].[Na+].O.Br[C:9]1[CH:17]=[C:16]2[C:12]([CH:13]=[N:14][NH:15]2)=[C:11]([NH:18][C:19]([C:21]2[N:22]=[C:23]([CH3:26])[S:24][CH:25]=2)=[O:20])[CH:10]=1.CC1(C)C(C)(C)OB([C:35]2[CH:43]=[CH:42][CH:41]=[C:40]3[C:36]=2[CH:37]=[CH:38][NH:39]3)O1>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[NH:39]1[C:40]2[C:36](=[C:35]([C:9]3[CH:17]=[C:16]4[C:12]([CH:13]=[N:14][NH:15]4)=[C:11]([NH:18][C:19]([C:21]4[N:22]=[C:23]([CH3:26])[S:24][CH:25]=4)=[O:20])[CH:10]=3)[CH:43]=[CH:42][CH:41]=2)[CH:37]=[CH:38]1

Participants

Conditions

Temperature: 150 °C

Procedure

2M Sodium carbonate solution (0.059 ml), Pd(dppf)Cl2 (5 mg), and water (1 ml) were added to solution of N-(6-bromo-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide (40 mg) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (35 mg) (Frontier Scientific) in 1,4-dioxane (1 ml). The reaction vessel was sealed and heated under microwave irradiation at 150° C. for 15 min. After cooling, water (4 ml) was added, and then the mixture was extracted into DCM (3×10 ml). The organic layers were combined and the solvent evaporated. The residue was dissolved in methanol:DMSO (0.5 ml, 1:1) and purified by mass directed preparative HPLC (Method A) to give title compound (16 mg).

Workup

customThe reaction vessel was sealed
temperatureAfter cooling
extractionthe mixture was extracted into DCM (3×10 ml)
customthe solvent evaporated
dissolutionThe residue was dissolved in methanol
customDMSO (0.5 ml, 1:1) and purified by mass

Sources & evidence

ORD record: ord-ecead1c48cc2455f971aa99bea7926f8
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658635B2

Reaction notes

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