Sodium hydride → HCID 86632299, compound

HRID 1929530Notes

Reaction equation

[C:1]([CH2:3][C:4]1[CH:5]=[CH:6][C:7]([F:12])=[C:8]([CH:11]=1)[C:9]#[N:10])#[N:2].[Cl:13][C:14]1[N:15]=[N:16][C:17](Cl)=[CH:18][C:19]=1[CH:20]([CH3:22])[CH3:21].[H-].[Na+]>C1COCC1>[Cl:13][C:14]1[N:15]=[N:16][C:17]([CH:3]([C:1]#[N:2])[C:4]2[CH:5]=[CH:6][C:7]([F:12])=[C:8]([CH:11]=2)[C:9]#[N:10])=[CH:18][C:19]=1[CH:20]([CH3:22])[CH3:21]

Participants

Conditions

Temperature: 0 °C

Procedure

To an ice-cold solution of 5-(cyanomethyl)-2-fluorobenzonitrile (1 eq) and 3,6-dichloro-4-isopropylpyridazine (1.3 eq) (Reference: Org. Prep.+Proc. Int. 1988, 20, 117 and U.S. Pat. No. 4,628,088, 1986) in THF (38 mL, 0.1 M) was added portionwise NaH (1 eq). The reaction was stirred at 0° C. for 15 min and then warmed to RT and stirred for 2 hrs. The reaction was quenched with a sat. aq. NaHCO3 and extracted with EtOAc. The combined organic fractions were washed with brine, dried (Na2SO4) and concentrated under reduced pressure. The crude was purified by silica gel chromatography, eluting with petroleum ether:EtOAc (8:2) to afford the title compound. 1H NMR (400 MHz, CDCl3) δ: 7.80-7.79 (2H, m), 7.49 (1H, s), 7.31-7.29 (1H, m), 5.63 (1H, s), 3.34-3.28 (1H, m), 1.36-1.29 (6H, m). MS (ES) C16H12ClFN4 required: 314/316. found: 315/317 (M+H)+.

Workup

temperaturewarmed to RT
stirringstirred for 2 hrs
customThe reaction was quenched with a sat. aq. NaHCO3
extractionextracted with EtOAc
washThe combined organic fractions were washed with brine
dry with materialdried (Na2SO4)
concentrationconcentrated under reduced pressure
customThe crude was purified by silica gel chromatography
washeluting with petroleum ether:EtOAc (8:2)

Sources & evidence

ORD record: ord-4676f021764847a682c5cf1f61d86b89
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08188084B2

Reaction notes

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