2,3-Diaminopyridine → 2-[1-(6-benzyl-4,5-dimethyl-pyridazin-3-yl)-piperidin-4-yl]-1H-imidazo[4,5-b]pyridine

HRID 1479973Notes

Reaction equation

[CH2:1]([C:8]1[N:13]=[N:12][C:11]([N:14]2[CH2:19][CH2:18][CH:17]([C:20](O)=O)[CH2:16][CH2:15]2)=[C:10]([CH3:23])[C:9]=1[CH3:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:25][C:26]1[C:31]([NH2:32])=[CH:30][CH:29]=[CH:28][N:27]=1>C(Cl)Cl>[CH2:1]([C:8]1[N:13]=[N:12][C:11]([N:14]2[CH2:19][CH2:18][CH:17]([C:20]3[NH:32][C:31]4[C:26]([N:25]=3)=[N:27][CH:28]=[CH:29][CH:30]=4)[CH2:16][CH2:15]2)=[C:10]([CH3:23])[C:9]=1[CH3:24])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

Conditions

Temperature: 150 °C

Procedure

To a solution of 1-(6-benzyl-4,5-dimethyl-pyridazin-3-yl)-piperidine-4-carboxylic acid (compound 26, 50 mg, 0.15 mmol) and 2,3-diaminopyridine (33 mg, 0.30 mmol) in CH2Cl2 (0.5 mL) is added polyphosphoric acid (1 mL). The mixture is concentrated to remove CH2Cl2. After being stirred at 150° C. for 1.5 h, the mixture is cooled to 25° C., diluted with water (10 mL), and basified by 10% aqueous solution of sodium hydroxide to pH˜8. The aqueous solution is extracted with CH2Cl2 (5×15 mL). The combined organic layers are concentrated and purified by HPLC (CH3CN/H2O: 22% 45% with 0.1% TFA) to give 2-[1-(6-benzyl-4,5-dimethyl-pyridazin-3-yl)-piperidin-4-yl]-1H-imidazo[4,5-b]pyridine (33.8 mg, 55%).

Workup

concentrationThe mixture is concentrated
customto remove CH2Cl2
temperaturethe mixture is cooled to 25° C.
additiondiluted with water (10 mL)
extractionThe aqueous solution is extracted with CH2Cl2 (5×15 mL)
concentrationThe combined organic layers are concentrated
custompurified by HPLC (CH3CN/H2O: 22% 45% with 0.1% TFA)

Sources & evidence

ORD record: ord-d028bbb948f8400c87c3081f630801f0
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409871B2

Reaction notes

Loading…