5-Trimethylstannanyl-indazole-1-carboxylic acid tert-butyl ester → 5-{4-bromo-5-[((1R,2R)-2-methyl-cyclopropanecarbonyl)-amino]-isothiazol-3-yl}-indazole-1-carboxylic acid tert-butyl ester

HRID 2079747Notes

Reaction equation

Br[C:2]1[C:6]([Br:7])=[C:5]([NH:8][C:9]([C@@H:11]2[CH2:13][C@H:12]2[CH3:14])=[O:10])[S:4][N:3]=1.[C:15]([O:19][C:20]([N:22]1[C:30]2[C:25](=[CH:26][C:27]([Sn](C)(C)C)=[CH:28][CH:29]=2)[CH:24]=[N:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:15]([O:19][C:20]([N:22]1[C:30]2[C:25](=[CH:26][C:27]([C:2]3[C:6]([Br:7])=[C:5]([NH:8][C:9]([C@@H:11]4[CH2:13][C@H:12]4[CH3:14])=[O:10])[S:4][N:3]=3)=[CH:28][CH:29]=2)[CH:24]=[N:23]1)=[O:21])([CH3:18])([CH3:16])[CH3:17]

Participants

Conditions

Temperature: 85 °C

Procedure

Dissolve (1R,2R)-2-methyl-cyclopropanecarboxylic acid (3,4-dibromo-isothiazol-5-yl)-amide (3.0; g, 8.82; mmol) in anhydrous 1,4-dioxane (88; mL) and add 5-trimethylstannanyl-indazole-1-carboxylic acid tert-butyl ester (4. 11; g, 9.70; mmol). Blanket under nitrogen, add bis(triphenylphosphine)palladium(II) chloride (0.62; g, 0.88 mmol) and heat to 85° C. for 4; days. Concentrate and purify the residue by silica gel chromatography, gradient eluting from 20:80; to 40:60; ethyl acetate:hexanes to give the title compound (1.04; g, 70% purity wt/wt, 17%) which is carried on with out further purification. MS (m/z): 477, 479; (M+1).

Workup

concentrationConcentrate
custompurify the residue by silica gel chromatography
washgradient eluting from 20:80

Sources & evidence

ORD record: ord-5f1ac936a29145f7a037ae4d10f2b7e5
Source dataset: uspto-grants-2011_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07932274B2

Reaction notes

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