Potassium Carbonate → N-[6-(5-Isoquinolinyl)-1H-indazol-4-yl]-2-methyl-1,3-thiazole-4-carboxamide

HRID 244735Notes

Reaction equation

[CH:1]1[C:10]2[C:5](=[C:6](B(O)O)[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.C(=O)([O-])[O-].[K+].[K+].Br[C:21]1[CH:29]=[C:28]2[C:24]([CH:25]=[N:26][NH:27]2)=[C:23]([NH:30][C:31]([C:33]2[N:34]=[C:35]([CH3:38])[S:36][CH:37]=2)=[O:32])[CH:22]=1>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]>[CH:1]1[C:10]2[C:5](=[C:6]([C:21]3[CH:29]=[C:28]4[C:24]([CH:25]=[N:26][NH:27]4)=[C:23]([NH:30][C:31]([C:33]4[N:34]=[C:35]([CH3:38])[S:36][CH:37]=4)=[O:32])[CH:22]=3)[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1

Participants

Conditions

Temperature: 150 °C

Procedure

5-Isoquinolinylboronic acid (21 mg), 0.6M potassium carbonate solution (200 μl) and Pd(dppf)Cl2 (10 mg) in 1,4-dioxane (1 ml) were treated with a solution of N-(6-bromo-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide (40 mg) in 1,4-dioxane (1 ml). The reaction vessel was sealed and heated under microwave irradiation at 150° C. for 30 min. After cooling the solvent was removed in vacuo. The sample was redissolved in methanol and loaded onto C18 reverse phase SPE (0.5 g). Product was eluted with acetonitrile/TFA (0.1%) (3×3 ml), and concentrated under a stream of nitrogen using blow down apparatus. Purification by mass directed preparative HPLC (Method C) gave the title compound.

Workup

customThe reaction vessel was sealed
temperatureAfter cooling the solvent
customwas removed in vacuo
dissolutionThe sample was redissolved in methanol
washProduct was eluted with acetonitrile/TFA (0.1%) (3×3 ml)
concentrationconcentrated under a stream of nitrogen using blow down apparatus
customPurification by mass

Sources & evidence

ORD record: ord-6029f44162404e2abec7cf39b4ad8617
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08658635B2

Reaction notes

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