1,4-Dioxane → 5-[4-(5-{[(2R,6S)-2,6-Dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-methyl-1H-indazol-6-yl]-2-(methyloxy)-3-pyridinamine

HRID 38850Notes

Reaction equation

Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][N:8]2[CH3:11])=[C:4]([C:12]2[O:13][C:14]([CH2:17][N:18]3[CH2:23][C@H:22]([CH3:24])[O:21][C@H:20]([CH3:25])[CH2:19]3)=[N:15][N:16]=2)[CH:3]=1.[CH3:26][O:27][C:28]1[C:33]([NH2:34])=[CH:32][C:31](B2OC(C)(C)C(C)(C)O2)=[CH:30][N:29]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1CCOCC1>[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].O>[CH3:25][C@H:20]1[O:21][C@@H:22]([CH3:24])[CH2:23][N:18]([CH2:17][C:14]2[O:13][C:12]([C:4]3[CH:3]=[C:2]([C:31]4[CH:32]=[C:33]([NH2:34])[C:28]([O:27][CH3:26])=[N:29][CH:30]=4)[CH:10]=[C:9]4[C:5]=3[CH:6]=[N:7][N:8]4[CH3:11])=[N:16][N:15]=2)[CH2:19]1

Participants

Conditions

Temperature: 100 °C

Procedure

6-Bromo-4-(5-{[(2R,6S)-2,6-dimethyl-4-morpholinyl]methyl}-1,3,4-oxadiazol-2-yl)-1-methyl-1H-indazole (200 mg, 0.492 mmol), 2-(methyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3-pyridinamine (123 mg, 0.492 mmol), 1,1′-bis(diphenylphosphino)ferrocene palladium dichloride (72.0 mg, 0.098 mmol) and tripotassium phosphate (313 mg, 1.477 mmol) were added to 1,4-dioxane (4 ml) and water (1 ml) then heated under microwave irradiation for 20 mins at 100° C. The solvent was removed under nitrogen and the crude residue purified by chromatography (20 g Si cartridge, gradient: 0-100% EtOAc/DCM +0-20% MeOH). The appropriate fractions were combined and the solvent was removed to give the title compound as a brown solid (130 mg).

Workup

customThe solvent was removed under nitrogen
customthe crude residue purified by chromatography (20 g Si cartridge, gradient: 0-100% EtOAc/DCM +0-20% MeOH)
customthe solvent was removed

Sources & evidence

ORD record: ord-419d4e31d0204233b6b86b5cfdba5422
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08524751B2

Reaction notes

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