Triethylamine → N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(chloromethyl)isoxazole-3-carboxamide

HRID 58526

Reaction equation

S(Cl)(Cl)=O.O[CH2:6][C:7]1[O:11][N:10]=[C:9]([C:12]([OH:14])=O)[CH:8]=1.[ClH:15].[Cl:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][CH:21]=[C:20]2[CH2:26][CH2:27][NH2:28].C(N(CC)CC)C>ClCCl>[Cl:16][C:17]1[CH:18]=[C:19]2[C:23](=[CH:24][CH:25]=1)[NH:22][CH:21]=[C:20]2[CH2:26][CH2:27][NH:28][C:12]([C:9]1[CH:8]=[C:7]([CH2:6][Cl:15])[O:11][N:10]=1)=[O:14]

Participants

Conditions

Temperature: 80 °C

Procedure

Thionyl chloride (0.5 mL; 7.26 mmol) was added to a mixture of 5-(hydroxymethyl)isoxazole-3-carboxylic acid (0.207 g; 7.26 mmol) and stirred at 80° C. for 72 h. The solution was concentrated under reduced pressure and the crude material was dissolved in dichloromethane (5 mL) and added to a mixture of 2-(5-chloro-1H-indol-3-yl)ethanamine hydrochloride (0.370 g; 1.60 mmol) and triethylamine (0.524 mL; 3.62 mmol) in dichloromethane (5 mL). The resulting solution was stirred at room temperature for 20 min, concentrated under reduced pressure and the crude material was purified by flash chromatography on silica gel (eluent 2 to 20% ethyl acetate in dichloromethane) to afford N-(2-(5-chloro-1H-indol-3-yl)ethyl)-5-(chloromethyl)isoxazole-3-carboxamide 0.088 g (22%).

Workup

concentrationThe solution was concentrated under reduced pressure
dissolutionthe crude material was dissolved in dichloromethane (5 mL)
stirringThe resulting solution was stirred at room temperature for 20 min
concentrationconcentrated under reduced pressure
customthe crude material was purified by flash chromatography on silica gel (eluent 2 to 20% ethyl acetate in dichloromethane)

Sources & evidence

ORD record: ord-e8aeaa6de6af4bfbb528e1622eee4e5b
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09434722B2

Linked notes

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