Hydrochloric Acid → 3-(4-{[(2-Methyl-1,3-thiazol-4-yl)carbonyl]amino}-1H-indazol-6-yl)benzoic acid

HRID 1695762Notes

Reaction equation

Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[C:4]([NH:11][C:12]([C:14]2[N:15]=[C:16]([CH3:19])[S:17][CH:18]=2)=[O:13])[CH:3]=1.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=2)[C:31]([OH:33])=[O:32])O1.C(=O)([O-])[O-].[Na+].[Na+].Cl>O1CCOCC1.O.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]>[CH3:19][C:16]1[S:17][CH:18]=[C:14]([C:12]([NH:11][C:4]2[CH:3]=[C:2]([C:28]3[CH:29]=[C:30]([CH:34]=[CH:35][CH:36]=3)[C:31]([OH:33])=[O:32])[CH:10]=[C:9]3[C:5]=2[CH:6]=[N:7][NH:8]3)=[O:13])[N:15]=1

Participants

Conditions

Temperature: 150 °C

Procedure

N-(6-Bromo-1H-indazol-4-yl)-2-methyl-1,3-thiazole-4-carboxamide (80 mg, 0.237 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoic acid (71 mg, 0.285 mmol), Pd(dppf)Cl2 (19 mg, 0.024 mmol) and 2 M sodium carbonate (aq) (0.356 ml, 0.712 mmol) were combined in 1,4-dioxane (1 ml) and water (1 ml). The reaction was heated in a Biotage microwave at 150° C. for 15 mins. The pH was adjusted to ˜2 with 2 M HCl (aq) and the solid formed was separated. The solid was extracted with 80% DCM in MeOH (3×25 ml) and the combined organic solvent was evaporated. The residue was dissolved in MeOH:DMSO (1 ml, 1:1, v/v) and purified by MDAP (Method B). The solvent of product-containing fractions was dried under a stream of nitrogen.

Workup

customthe solid formed
customwas separated
extractionThe solid was extracted with 80% DCM in MeOH (3×25 ml)
customthe combined organic solvent was evaporated
dissolutionThe residue was dissolved in MeOH
customDMSO (1 ml, 1:1, v/v) and purified by MDAP (Method B)
customThe solvent of product-containing fractions was dried under a stream of nitrogen

Sources & evidence

ORD record: ord-39dcf24c38794489be07bd0ca792a3d8
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08163743B2

Reaction notes

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