Sodium Carbonate → 5-(6-cyclopropylpyrazin-2-yl)-1H-indazole

HRID 1529372Notes

Reaction equation

Br[C:2]1[CH:7]=[N:6][CH:5]=[C:4]([CH:8]2[CH2:10][CH2:9]2)[N:3]=1.CC1(C)C(C)(C)OB([C:19]2[CH:20]=[C:21]3[C:25](=[CH:26][CH:27]=2)[NH:24][N:23]=[CH:22]3)O1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:8]1([C:4]2[N:3]=[C:2]([C:19]3[CH:20]=[C:21]4[C:25](=[CH:26][CH:27]=3)[NH:24][N:23]=[CH:22]4)[CH:7]=[N:6][CH:5]=2)[CH2:10][CH2:9]1

Participants

Conditions

Temperature: 100 °C

Procedure

A reaction vessel was charged with 2-bromo-6-cyclopropylpyrazine (1.27 g, 6.39 mmol, Combi-Phos Catalysts Inc.) and Pd(PPh3)4 (308 mg, 0.27 mmol). The tube was sealed. A solution of 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (1.30 g, 5.33 mmol) in dioxane (18 mL) and 2 M Na2CO3 (aq.) (8.0 mL, 16.0 mmol) were added. The reaction was stirred and heated at 100° C. overnight. After cooling to RT, the organic layer was separated and dried over anhydrous Na2SO4, filtered and concentrated. The crude was purified by silica gel chromatography, eluting with a gradient of 0-50% EtOAc in hexanes, to provide 5-(6-cyclopropylpyrazin-2-yl)-1H-indazole (575 m g, 2.43 mmol, 46% yield) as an off-white solid. MS (ESI, pos. ion) m/z: 237.2 (M+1).

Workup

customThe tube was sealed
temperatureAfter cooling to RT
customthe organic layer was separated
dry with materialdried over anhydrous Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude was purified by silica gel chromatography
washeluting with a gradient of 0-50% EtOAc in hexanes

Sources & evidence

ORD record: ord-2313e9c261c34a139d745733df2e4f6b
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09090593B2

Reaction notes

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