N,N-Dimethyl-1,3-propanediamine → 2-[5-(4-Benzyloxy-3,5-dimethyl-phenyl)-[1,3,4]oxadiazol-2-yl]-6-isobutyl-4-methoxy-pyridine

HRID 2037363Notes

Reaction equation

HRID 2037363 reaction equation
[CH2:1]([C:5]1[N:10]=[C:9]([C:11]([OH:13])=O)[CH:8]=[C:7]([O:14][CH3:15])[CH:6]=1)[CH:2]([CH3:4])[CH3:3].[CH2:16]([O:23][C:24]1[C:33]([CH3:34])=[CH:32][C:27]([C:28]([NH:30][NH2:31])=O)=[CH:26][C:25]=1[CH3:35])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.CCN(C(C)C)C(C)C.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.CN(C)CCCN>C(Cl)Cl.C(OCC)C.N1C=CC=CC=1>[CH2:16]([O:23][C:24]1[C:25]([CH3:35])=[CH:26][C:27]([C:28]2[O:13][C:11]([C:9]3[CH:8]=[C:7]([O:14][CH3:15])[CH:6]=[C:5]([CH2:1][CH:2]([CH3:3])[CH3:4])[N:10]=3)=[N:31][N:30]=2)=[CH:32][C:33]=1[CH3:34])[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

10

Reactant 6

HCID 7993N,N-Dimethyl-1,3-propanediamineHCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 2724699PyBOPHCID 584181026-Isobutyl-4-methoxy-pyridine-2-carboxylic acidHCID 592020304-Benzyloxy-3,5-dimethylbenzoic acid hydrazide

Product 1

HCID 686303802-[5-(4-Benzyloxy-3,5-dimethyl-phenyl)-[1,3,4]oxadiazol-2-yl]-6-isobutyl-4-methoxy-pyridineYield 84.9%

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 6-isobutyl-4-methoxy-pyridine-2-carboxylic acid (270 mg, 1.10 mmol), 4-benzyloxy-3,5-dimethyl-benzoic acid hydrazide (327 mg, 1.21 mmol) and DIPEA (455 mg, 3.52 mmol) in DCM (15 mL), PyBOP (858 mg, 1.65 mmol) is added at 0° C. The mixture is stirred for 30 min at rt, the reaction is diluted with diethyl ether and washed with 1 N aq. NaOH solution followed by 1 M aq. NaH2PO4 solution. The org. extract is dried over Na2SO4, filtered and concentrated to give the crude hydrazide intermediate; LC-MS: tR=1.00 min, [M+H]+=462.23. This material (1.13 g) is dissolved in DCM (15 mL) and pyridine (1 mL) and the mixture is cooled to 0° C. before trifluoromethanesulfonic anhydride (1.38 g, 4.89 mmol) is added dropwise. The mixture is warmed to rt and stirring is continued for 16 h. The reaction is quenched by adding 3-dimethylamino-1-propylamine (50 mg, 0.49 mmol). The mixture is washed twice with 1 N aq. NaH2PO4 solution followed by water, dried over Na2SO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 4:1 to give 2-[5-(4-benzyloxy-3,5-dimethyl-phenyl)-[1,3,4]oxadiazol-2-yl]-6-isobutyl-4-methoxy-pyridine (414 mg) as a yellow oil; LC-MS: tR=1.15 min, [M+H]+=444.21.

Workup

  1. washwashed with 1 N aq. NaOH solution
  2. extractionextract
  3. dry with materialis dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude hydrazide intermediate
  7. additionis added dropwise
  8. temperatureThe mixture is warmed to rt
  9. stirringstirring
  10. waitis continued for 16 h
  11. customThe reaction is quenched
  12. washThe mixture is washed twice with 1 N aq. NaH2PO4 solution
  13. dry with materialdried over Na2SO4
  14. filtrationfiltered
  15. concentrationconcentrated
  16. customThe crude product is purified by CC on silica gel eluting with heptane:EA 4:1

Sources & evidence

ORD record
ord-d374f1a7900a47969e0599432c963d0f
Source dataset
uspto-grants-2013_11
Patent number
US08575200B2

Reaction notes

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