Diisopropylethylamine → 4-[5-(4-Benzyloxy-3-ethyl-5-methyl-phenyl)-[1,2,4]oxadiazol-3-yl]-2-cyclopentyl-6-methoxy-pyridine

HRID 245116Notes

Reaction equation

HRID 245116 reaction equation
[CH:1]1([C:6]2[CH:7]=[C:8]([CH:13]=[C:14]([O:16][CH3:17])[N:15]=2)[C:9]([NH:11][OH:12])=[NH:10])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH2:18]([O:25][C:26]1[C:34]([CH3:35])=[CH:33][C:29]([C:30](O)=O)=[CH:28][C:27]=1[CH2:36][CH3:37])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>C(Cl)Cl.CC(=O)OCC.O>[CH2:18]([O:25][C:26]1[C:34]([CH3:35])=[CH:33][C:29]([C:30]2[O:12][N:11]=[C:9]([C:8]3[CH:13]=[C:14]([O:16][CH3:17])[N:15]=[C:6]([CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5]4)[CH:7]=3)[N:10]=2)=[CH:28][C:27]=1[CH2:36][CH3:37])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 594979194-Benzyloxy-3-ethyl-5-methyl-benzoic acidHCID 178492422HCID 178492422, compound

Product 1

HCID 674912534-[5-(4-Benzyloxy-3-ethyl-5-methyl-phenyl)-[1,2,4]oxadiazol-3-yl]-2-cyclopentyl-6-methoxy-pyridineYield 59.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-cyclopentyl-N-hydroxy-6-methoxy-isonicotinamidine (870 mg, 3.70 mmol), 4-benzyloxy-3-ethyl-5-methyl-benzoic acid (1.00 g, 3.70 mmol) and DIPEA (1.44 g, 11.1 mmol) in DCM (30 mL), TBTU (1.43 g, 4.44 mmol) is added. The mixture is stirred at rt for 1 h before diluted with EA (150 mL) and water (50 mL). The org. phase is separated, washed with sat. aq. NaHCO3 solution (50 mL) followed by brine (50 mL), dried over MgSO4, filtered and concentrated. The remaining pale brown oil is dissolved in dioxane (40 mL) and then stirred at 115° C. for 48 h. The solvent is evaporated and the crude product is purified by CC on silica gel eluting with heptane:EA 1:9 to give 4-[5-(4-benzyloxy-3-ethyl-5-methyl-phenyl)-[1,2,4]oxadiazol-3-yl]-2-cyclopentyl-6-methoxy-pyridine (1040 mg) as a pale yellow oil; LC-MS**: tR=1.11 min, [M+H]+=470.26.

Workup

  1. customphase is separated
  2. washwashed with sat. aq. NaHCO3 solution (50 mL)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe remaining pale brown oil is dissolved in dioxane (40 mL)
  7. stirringstirred at 115° C. for 48 h
  8. customThe solvent is evaporated
  9. customthe crude product is purified by CC on silica gel eluting with heptane:EA 1:9

Sources & evidence

ORD record
ord-2262d6520dd744b68658c9e80b3951ab
Source dataset
uspto-grants-2014_02
Patent number
US08658675B2

Reaction notes

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