N-methyl-2-pyrrolidone → 6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-4-carbonitrile

HRID 475131Notes

Reaction equation

Br[C:2]1[CH:10]=[C:9]([CH3:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1.[CH3:18][N:19]1C(=O)CCC1>[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>[CH3:11][C:9]1[CH:10]=[C:2]([C:18]#[N:19])[C:3]2[CH:4]=[N:5][N:6]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[C:7]=2[CH:8]=1

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 4-bromo-6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (1.1 g, 3.74 mmol), Zn(CN)2 (873 mg, 7.46 mmol), and Pd(PPh3)4 (646 mg, 0.56 mmol) in NMP (25 mL) under nitrogen was heated at 100° C. overnight. After it was cooled to RT, the reaction mixture was partitioned between EtOAc (300 mL) and water (50 mL). The organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. The residue was purified by silica gel chromatography using petroleum ether:EtOAc (10:1) as eluting solvents to afford 6-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-4-carbonitrile as white solid (400 mg, 50%). MS (ESI): m/z=242.3 [M+1]+.

Workup

temperatureAfter it was cooled to RT
customthe reaction mixture was partitioned between EtOAc (300 mL) and water (50 mL)
washThe organic layer was washed with brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo
customThe residue was purified by silica gel chromatography
washas eluting solvents

Sources & evidence

ORD record: ord-d99f1e01624742aa9fb420f5cca0b0aa
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637537B2

Reaction notes

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