Isopropylamine → 2-[2-(3-Butyl-5-methyl-isoxazol-4-yl)-ethyl]-thiazole-5-carboxylic acid isopropylamide

HRID 1923554Notes

Reaction equation

[CH:1]([NH2:4])([CH3:3])[CH3:2].C[Al](C)C.C[O:10][C:11]([C:13]1[S:17][C:16]([CH2:18][CH2:19][C:20]2[C:21]([CH2:26][CH2:27][CH2:28][CH3:29])=[N:22][O:23][C:24]=2[CH3:25])=[N:15][CH:14]=1)=O>O1CCOCC1.C1(C)C=CC=CC=1>[CH:1]([NH:4][C:11]([C:13]1[S:17][C:16]([CH2:18][CH2:19][C:20]2[C:21]([CH2:26][CH2:27][CH2:28][CH3:29])=[N:22][O:23][C:24]=2[CH3:25])=[N:15][CH:14]=1)=[O:10])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 90 °C

Procedure

To a stirred solution of isopropylamine (130 mg, 2.2 mmol) in dioxane (3 mL) under argon and at room temperature was added trimethylaluminium (0.65 mL of a 2M solution in toluene, 1.3 mmol). After 1 h, a solution of 2-[2-(3-butyl-5-methyl-isoxazol-4-yl)-ethyl]-thiazole-5-carboxylic acid methyl ester (170 mg, 0.55 mmol) in dioxane (3 mL) was added and the reaction mixture heated at 90° C. overnight. The reaction mixture was then cooled, quenched with ice water and extracted with dichloromethane. The combined extracts were washed with Seignette's salt solution then dried, filtered, and concentrated. Purification by chromatography (silica, 0 to 6% methanol in dichloromethane then heptane:ethyl acetate=100:0 to 1:4) gave the title compound (30 mg, 16%) as a white solid. MS: m/e=336.5 [M+H]+.

Workup

temperatureThe reaction mixture was then cooled
customquenched with ice water
extractionextracted with dichloromethane
washThe combined extracts were washed with Seignette's salt solution
customthen dried
filtrationfiltered
concentrationconcentrated
customPurification by chromatography (silica, 0 to 6% methanol in dichloromethane

Sources & evidence

ORD record: ord-48f991faec5c427c83fbced784797f37
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08178522B2

Reaction notes

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