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

HRID 2047332Notes

Reaction equation

HRID 2047332 reaction equation
[CH2:1]([N:3]([CH2:14][CH3:15])[C:4]1[CH:5]=[C:6]([CH:10]=[C:11]([CH3:13])[N:12]=1)[C:7]([OH:9])=O)[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:47]([O:54][C:55]1[C:64]([CH3:65])=[CH:63][C:58]([C:59]([NH:61][NH2:62])=[O:60])=[CH:57][C:56]=1[CH2:66][CH3:67])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>C(Cl)Cl.CN(C=O)C>[CH2:14]([N:3]([CH2:1][CH3:2])[C:4]1[CH:5]=[C:6]([C:7]([NH:62][NH:61][C:59](=[O:60])[C:58]2[CH:63]=[C:64]([CH3:65])[C:55]([O:54][CH2:47][C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=3)=[C:56]([CH2:66][CH3:67])[CH:57]=2)=[O:9])[CH:10]=[C:11]([CH3:13])[N:12]=1)[CH3:15]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 584180552-(Diethylamino)-6-methylisonicotinic acidHCID 592020264-Benzyloxy-3-ethyl-5-methyl-benzoic acid hydrazide

Product 1

HCID 685803094-benzyloxy-3-ethyl-5-methyl-benzoic acid N'-(2-diethylamino-6-methyl-pyridine-4-carbonyl)-hydrazideYield 72.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-f32c5f7b976b427fbdb155ab1c09a92f
Source dataset
uspto-grants-2013_11
Patent number
US08592460B2

Reaction notes

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