Dimethylformamide → 6-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-4-carbonitrile

HRID 475162Notes

Reaction equation

Br[C:2]1[CH:10]=[C:9]([O:11][CH3:12])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH:13]1[CH2:18][CH2:17][CH2:16][CH2:15][O:14]1.[CH3:19][N:20](C=O)C>[C-]#N.[C-]#N.[Zn+2].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>[CH3:12][O:11][C:9]1[CH:10]=[C:2]([C:19]#[N:20])[C:3]2[CH:4]=[N:5][N:6]([CH:13]3[CH2:18][CH2:17][CH2:16][CH2:15][O:14]3)[C:7]=2[CH:8]=1

Participants

Conditions

Temperature: 145 °C

Procedure

A sealed microwave vial was charged with 4-bromo-6-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (1.50 g, 4.82 mmol), Zn(CN)2 (0.62 g, 5.30 mmol), Pd(PPh3)4 (0.22 g, 0.19 mmol), and DMF (13 mL). The mixture was degassed for 5 min under nitrogen and then heated in a microwave reactor at 145° C. for 25 min. The mixture was diluted with EtOAc and filtered. The filtrate was partitioned between water and EtOAc, and the layers were separated. The organic layer was washed with water (3×), dried (Na2SO4), filtered, and concentrated in vacuo. The crude mixture was purified by SiO2 chromatography to afford 6-methoxy-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-4-carbonitrile as a solid (1.06 g, 86%). MS (ESI) m/z: 258.2 [M+1]+.

Workup

customThe mixture was degassed for 5 min under nitrogen
additionThe mixture was diluted with EtOAc
filtrationfiltered
customThe filtrate was partitioned between water and EtOAc
customthe layers were separated
washThe organic layer was washed with water (3×)
dry with materialdried (Na2SO4)
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude mixture was purified by SiO2 chromatography

Sources & evidence

ORD record: ord-21c7529ae68c47449bb2c436c7520d4b
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637537B2

Reaction notes

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