Diisopropylethylamine → HCID 136391016, compound

HRID 245106Notes

Reaction equation

HRID 245106 reaction equation
[CH2:1]([CH:3]([C:6]1[CH:7]=[C:8]([CH:12]=[C:13]([O:15][CH3:16])[N:14]=1)[C:9]([OH:11])=O)[CH2:4][CH3:5])[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.[CH2:48]([C:50]1[CH:51]=[C:52]([CH:57]=[C:58]([CH3:61])[C:59]=1[OH:60])[C:53]([NH:55]O)=[NH:54])[CH3:49]>CN(C=O)C.C(Cl)Cl>[CH2:48]([C:50]1[CH:51]=[C:52]([C:53]2[N:55]=[C:9]([C:8]3[CH:12]=[C:13]([O:15][CH3:16])[N:14]=[C:6]([CH:3]([CH2:1][CH3:2])[CH2:4][CH3:5])[CH:7]=3)[O:11][N:54]=2)[CH:57]=[C:58]([CH3:61])[C:59]=1[OH:60])[CH3:49]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 584181082-(1-Ethylpropyl)-6-methoxyisonicotinic acidHCID 178436626HCID 178436626, compound

Product 1

HCID 136391016HCID 136391016, compoundYield 47.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-(1-ethyl-propyl)-6-methoxy-isonicotinic acid (436 mg, 1.95 mmol) and DIPEA (759 mg, 5.86 mmol) in DMF (30 mL), TBTU (627 mg, 1.95 mmol) is added. The mixture is stirred at rt for 15 min before 3-ethyl-4,N-dihydroxy-5-methyl-benzamidine (379 mg, 1.95 mmol) is added. Stirring is continued at rt for 2 h. The mixture is diluted with DCM (100 mL) and washed three times with sat. aq. NaHCO3 solution. The org. extract is dried over MgSO4, filtered and concentrated. The residue is dissolved in dioxane (20 mL) and the mixture is stirred at 100° C. for 18 h. The mixture is concentrated and the crude product is purified by prep. HPLC to give 2-ethyl-4-{5-[2-(1-ethyl-propyl)-6-methoxy-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenol (355 mg) as a beige solid; LC-MS: tR=1.20 min, [M+H]+=382.04; 1H NMR (CDCl3): δ0.84 (t, J=7.3 Hz, 6H), 1.34 (t, J=7.5 Hz, 3H), 1.68-1.89 (m, 4H), 2.36 (s, 3H), 2.57-2.65 (m, 1H), 2.74 (q, J=7.8 Hz, 2H), 4.02 (s, 3H), 5.00 (s br, 1H), 7.33 (s, 1H), 7.45 (s, 1H), 7.85 (s, 2H).

Workup

  1. additionis added
  2. washwashed three times with sat. aq. NaHCO3 solution
  3. extractionextract
  4. dry with materialis dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dissolutionThe residue is dissolved in dioxane (20 mL)
  8. stirringthe mixture is stirred at 100° C. for 18 h
  9. concentrationThe mixture is concentrated
  10. customthe crude product is purified by prep

Sources & evidence

ORD record
ord-12eaa4d43f414ca891013d94d6ec449c
Source dataset
uspto-grants-2014_02
Patent number
US08658675B2

Reaction notes

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