Isopropylamine → 6-(3-Butyl-5-methyl-isoxazol-4-ylmethoxy)-pyridazine-3-carboxylic acid isopropylamide

HRID 1958069Notes

Reaction equation

C[Al](C)C.[CH:5]([NH2:8])([CH3:7])[CH3:6].C[O:10][C:11]([C:13]1[N:14]=[N:15][C:16]([O:19][CH2:20][C:21]2[C:22]([CH2:27][CH2:28][CH2:29][CH3:30])=[N:23][O:24][C:25]=2[CH3:26])=[CH:17][CH:18]=1)=O>C1(C)C=CC=CC=1.O1CCOCC1>[CH:5]([NH:8][C:11]([C:13]1[N:14]=[N:15][C:16]([O:19][CH2:20][C:21]2[C:22]([CH2:27][CH2:28][CH2:29][CH3:30])=[N:23][O:24][C:25]=2[CH3:26])=[CH:17][CH:18]=1)=[O:10])([CH3:7])[CH3:6]

Participants

Conditions

Temperature: 90 °C

Procedure

Trimethylaluminium (0.72 mL of a 2 M solution in toluene, 1.44 mmol) was added dropwise to a stirred solution of isopropylamine (85 mg, 1.44 mmol) in dioxane (3 mL) at room temperature under argon. After 1 h, a solution of 6-(3-butyl-5-methyl-isoxazol-4-ylmethoxy)-pyridazine-3-carboxylic acid methyl ester (110 mg, 0.36 mmol) in dioxane (3 mL) was added and the reaction mixture heated at 90° C. After 2 h the reaction mixture was cooled in an ice/water bath and quenched with Seignette salt solution (1 mL). The resultant mixture was filtered, the filter cake washed with dichloromethane, then the combined filtrates were concentrated then purified by chromatography (silica, 0 to 80% ethyl acetate in heptane) to give the title compound (45 mg, 38%) as a colourless oil. MS: m/e=333.4 [M+H]+.

Workup

temperatureAfter 2 h the reaction mixture was cooled in an ice/water bath
customquenched with Seignette salt solution (1 mL)
filtrationThe resultant mixture was filtered
washthe filter cake washed with dichloromethane
concentrationthe combined filtrates were concentrated
customthen purified by chromatography (silica, 0 to 80% ethyl acetate in heptane)

Sources & evidence

ORD record: ord-fe949e606ecb4bb8a1293d99331bf34a
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08410104B2

Reaction notes

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