3-Chloro-6-methylpyridazine → HCID 24967301, compound

HRID 655306Notes

Reaction equation

[N:1]1[C:10]2[C:5](=[CH:6][C:7]([CH:11]([CH3:16])[C:12]([NH:14][NH2:15])=O)=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Cl[C:18]1[N:19]=[N:20][C:21]([CH3:24])=[CH:22][CH:23]=1>C(O)CCC>[CH3:24][C:21]1[CH:22]=[CH:23][C:18]2[N:14]([C:12]([CH:11]([C:7]3[CH:6]=[C:5]4[C:10](=[CH:9][CH:8]=3)[N:1]=[CH:2][CH:3]=[CH:4]4)[CH3:16])=[N:20][N:19]=2)[N:15]=1

Participants

Conditions

Temperature: 120 °C

Procedure

2-Quinolin-6-yl-propionic acid hydrazide (intermediate 63) (500 mg, 2.32 mmol) was added to a stirred solution of 3-chloro-6-methylpyridazine (299 mg, 2.32 mmol) in n-butanol. The reaction mixture was heated at 120° C., overnight. The volatiles were removed in vacuo and the residue absorbed onto silica gel and purified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-90:10) to obtain 6-[1-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)-ethyl]-quinoline (356 mg, 53% yield). To 6-[1-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)-ethyl]-quinoline (356 mg, 1.23 mmol) was added a dropwise solution of bromine (1.73 uL, 3.69 mmol) in acetic acid (3 mL). The reaction was heated at 100° C. for 2 hours. The reaction mixture was cooled to room temperature and the solvent removed in vacuo. A solution of 10% aq. NaSH (10 mL) was added and the product extracted with 10% methanol in dichloromethane. The organic phase was washed with 5% aqueous sodium sulfite. The filtrate was then concentrated in vacuo onto silica gel and purified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-90:10) to return the title compound (168 mg, 37% yield). Analytical data presented in Table 1.

Workup

customThe volatiles were removed in vacuo
customthe residue absorbed onto silica gel
custompurified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-90:10)

Sources & evidence

ORD record: ord-cf0eea51e46b480e8b55a143c8ceea56
Source dataset: uspto-grants-2011_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08071581B2

Reaction notes

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