N-methyl-2-pyrrolidone → 6-chloro-2-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole-4-carbonitrile

HRID 475128Notes

Reaction equation

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

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 4-bromo-6-chloro-2-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole (3.2 g, 9.70 mmol), Zn(CN)2 (2.3 g, 19.40 mmol), and Pd(PPh3)4 (1.1 g, 0.97 mmol) in NMP (20 mL) was stirred at 90° C. for 3 h. The reaction mixture was filtered and the filtrate diluted with EtOAc (50 mL). The organic layer was washed with water (50 mL×3), dried (MgSO4) and concentrated in vacuo. The residue was purified by SiO2 chromatography eluting with a DCM/MeOH gradient (0 to 6% MeOH) to afford 6-chloro-2-methyl-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazole-4-carbonitrile as a white solid (1.0 g, 37.2%). MS (ESI): m/z=276.2 [M+1]+.

Workup

filtrationThe reaction mixture was filtered
additionthe filtrate diluted with EtOAc (50 mL)
washThe organic layer was washed with water (50 mL×3)
dry with materialdried (MgSO4)
concentrationconcentrated in vacuo
customThe residue was purified by SiO2 chromatography
washeluting with a DCM/MeOH gradient (0 to 6% MeOH)

Sources & evidence

ORD record: ord-97b3b702464b4e0a8fccaeb4f3f85562
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637537B2

Reaction notes

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