Diisopropylethylamine → 4-benzyloxy-3-ethyl-5-methyl-benzoic acid N'-(2-diethylamino-6-methyl-pyridine-4-carbonyl)-hydrazide

To a solution of 2-diethylamino-6-methyl-isonicotinic acid (1.50 g, 6.13 mmol) and DIPEA (2.38 g, 18.4 mmol) in DCM (25 mL), TBTU (2.16 g, 6.74 mmol) is added. The mixture is stirred at rt for 10 min before a solution of 4-benzyloxy-3-ethyl-5-methyl-benzoic acid hydrazide (3.32 g, 6.13 mmol) in DMF (10 mL) is added. The mixture is stirred at rt for 1 h before it is diluted with DCM and washed with sat. aq. NaHCO3-solution. The org. extract is dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with a gradient of EA in heptane to give 4-benzyloxy-3-ethyl-5-methyl-benzoic acid N′-(2-diethylamino-6-methyl-pyridine-4-carbonyl)-hydrazide (2.1 g) as a gum; LC-MS: tR=0.88 min, [M+1]+=not detectable. This material (2.10 g, 4.42 mmol) is dissolved in THF (40 mL) and Burgess reagent (1.16 g, 4.87 mmol) is added. The mixture is stirred at 110° C. for 5 min under microwave irradiation. The mixture is cooled to rt, diluted with diethyl ether and washed with water. The org. extract is dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 4:1 to give {4-[5-(4-benzyloxy-3-ethyl-5-methyl-phenyl)-[1,3,4]oxadiazol-2-yl]-6-methyl-pyridin-2-yl}-diethyl-amine (1.03 g) as a pale yellow gum; LC-MS: tR=0.99 min, [M+1]+=457.27.

1. additionis added
2. washwashed with sat. aq. NaHCO3-solution
3. extractionextract
4. dry with materialis dried over MgSO4
5. filtrationfiltered
6. concentrationconcentrated
7. customThe crude product is purified by CC on silica gel eluting with a gradient of EA in heptane

ORD record

ord-f32c5f7b976b427fbdb155ab1c09a92f

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592460B2