Carbon Tetrachloride → 3-benzyl-6-[4-(5-chloro-1H-imidazol-2-yl)-piperidin-1-yl]-4,5-dimethyl-pyridazine

HRID 1479972Notes

Reaction equation

[C:1]([CH2:3][NH:4][C:5]([CH:7]1[CH2:12][CH2:11][N:10]([C:13]2[N:14]=[N:15][C:16]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)=[C:17]([CH3:20])[C:18]=2[CH3:19])[CH2:9][CH2:8]1)=O)#[N:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(Cl)(Cl)(Cl)[Cl:48]>C(#N)C>[CH2:21]([C:16]1[N:15]=[N:14][C:13]([N:10]2[CH2:11][CH2:12][CH:7]([C:5]3[NH:2][C:1]([Cl:48])=[CH:3][N:4]=3)[CH2:8][CH2:9]2)=[C:18]([CH3:19])[C:17]=1[CH3:20])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of 1-(6-benzyl-4,5-dimethyl-pyridazin-3-yl)-piperidine-4-carboxylic acid cyanomethyl-amide (20 mg, 0.055 mmol) and triphenyl phosphine in acetonitrile (1 mL) at 25° C. is added carbon tetrachloride (42 mg, 0.28 mmol). After being stirred at 50° C. for 3 h, the mixture is concentrated, and diluted with CH2Cl2 (10 mL) and washed with sodium hydroxide (2 mL, 1N), and H2O (2 mL), dried over Na2SO4, filtered and concentrated. The crude product is purified by HPLC (CH3CN/H2O: 22%˜45% with 0.1% TFA) to give 3-benzyl-6-[4-(5-chloro-1H-imidazol-2-yl)-piperidin-1-yl]-4,5-dimethyl-pyridazine (11.8 mg, 56%).

Workup

concentrationthe mixture is concentrated
additiondiluted with CH2Cl2 (10 mL)
washwashed with sodium hydroxide (2 mL, 1N), and H2O (2 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customThe crude product is purified by HPLC (CH3CN/H2O: 22%˜45% with 0.1% TFA)

Sources & evidence

ORD record: ord-354fbe399fba42148f53101a92e35092
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409871B2

Reaction notes

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