Diisopropylethylamine → HCID 136170273, compound

HRID 2065914Notes

Reaction equation

HRID 2065914 reaction equation
Cl.[CH2:2]([C:4]1[C:5]([CH2:13][CH3:14])=[N:6][CH:7]=[C:8]([CH:12]=1)[C:9]([OH:11])=O)[CH3:3].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH2:46]([C:48]1[CH:49]=[C:50]([CH:55]=[C:56]([CH3:59])[C:57]=1[OH:58])[C:51]([NH:53]O)=[NH:52])[CH3:47]>C(Cl)Cl>[CH2:2]([C:4]1[CH:12]=[C:8]([C:9]2[O:11][N:53]=[C:51]([C:50]3[CH:55]=[C:56]([CH3:59])[C:57]([OH:58])=[C:48]([CH2:46][CH3:47])[CH:49]=3)[N:52]=2)[CH:7]=[N:6][C:5]=1[CH2:13][CH3:14])[CH3:3]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 67027015HCID 67027015, compoundHCID 178436626HCID 178436626, compound

Product 1

HCID 136170273HCID 136170273, compoundYield 28.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 5,6-diethyl-nicotinic acid hydrochloride (920 mg, 4.3 mmol) and Hünig's base (2.76 g, 21 mmol) in DCM (50 mL) is added TBTU (1.785 g, 5.55 mmol) and the mixture is stirred at rt for 5 min. 3-Ethyl-4,N-dihydroxy-5-methyl-benzamidine (1.14 g, 4.7 mmol) is added and the mixture stirred for 0.5 h. The mixture is diluted with DCM, washed with sat. aq. NaHCO3 solution, dried over MgSO4, filtered and concentrated. The crude 5,6-diethyl-nicotinic acid (3-ethyl-4,N-dihydroxy-5-methyl-benzamidine) ester (LC-MS: tR=0.79 min) is dissolved in dioxane (50 mL) and heated to 100° C. for 18 h. The solvent is evaporated and the crude product is purified by FC on silica gel eluting with heptane:EA 10:1 to give 4-[5-(5,6-diethyl-pyridin-3-yl)-[1,2,4]oxadiazol-3-yl]-2-ethyl-6-methyl-phenol (0.42 g) as a solid; LC-MS: tR=1.03 min, [M+1]+=338.09.

Workup

  1. stirringthe mixture stirred for 0.5 h
  2. washwashed with sat. aq. NaHCO3 solution
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe crude 5,6-diethyl-nicotinic acid (3-ethyl-4,N-dihydroxy-5-methyl-benzamidine) ester (LC-MS: tR=0.79 min) is dissolved in dioxane (50 mL)
  7. temperatureheated to 100° C. for 18 h
  8. customThe solvent is evaporated
  9. customthe crude product is purified by FC on silica gel eluting with heptane:EA 10:1

Sources & evidence

ORD record
ord-76625bef59204222b60b49a4028b7406
Source dataset
uspto-grants-2012_10
Patent number
US08288554B2

Reaction notes

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