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

HRID 245122Notes

Reaction equation

HRID 245122 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][NH2:12])=[O: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.CC[N+](S(N=C(OC)[O-])(=O)=O)(CC)CC>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:10][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:11][N:12]=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

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 2724994Methyl N-(triethylammoniosulfonyl)carbamateHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 594979194-Benzyloxy-3-ethyl-5-methyl-benzoic acidHCID 674911922-Cyclopentyl-6-methoxy-isonicotinic acid hydrazide

Product 1

HCID 674913324-[5-(4-Benzyloxy-3-ethyl-5-methyl-phenyl)-[1,3,4]oxadiazol-2-yl]-2-cyclopentyl-6-methoxy-pyridineYield 43.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 2-cyclopentyl-6-methoxy-isonicotinic acid hydrazide (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 yellow oil is dissolved in THF (50 mL) and Burgess reagent (1.23 g, 5.18 mmol) is added. The mixture is stirred at 110° C. for 15 min under microwave irradiation before it is diluted with EA (200 mL) and washed twice with water (50 mL). The org. extract is dried over MgSO4, filtered and concentrated 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)-[1,3,4]oxadiazol-2-yl]-2-cyclopentyl-6-methoxy-pyridine (750 mg) as a pale yellow oil; LC-MS**: tR=1.06 min, [M+H]+=470.21.

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 yellow oil is dissolved in THF (50 mL)
  7. stirringThe mixture is stirred at 110° C. for 15 min under microwave irradiation before it
  8. washwashed twice with water (50 mL)
  9. extractionextract
  10. dry with materialis dried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customthe crude product is purified by CC on silica gel eluting with heptane:EA 1:9

Sources & evidence

ORD record
ord-a30981e6479544f49df826a0741b659e
Source dataset
uspto-grants-2014_02
Patent number
US08658675B2

Reaction notes

Loading…