Isonicotinic Acid → HCID 68554551, compound

HRID 2040825Notes

Reaction equation

HRID 2040825 reaction equation
C(O)(=O)[C:2]1[CH:7]=[CH:6]N=CC=1.[CH2:10]([O:17][C:18]1[C:27]([CH3:28])=[CH:26][C:21]([C:22]([NH:24][NH2:25])=O)=[CH:20][C:19]=1[CH2:29][CH3:30])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.CC[N:33](C(C)C)[CH:34]([CH3:36])[CH3:35].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:82])=CC=1.[CH2:95]1[CH2:99]O[CH2:97][CH2:96]1>C(Cl)Cl.CC(=O)OCC>[CH2:10]([O:17][C:18]1[C:27]([CH3:28])=[CH:26][C:21]([C:22]2[S:82][C:97]([C:96]3[CH:35]=[C:34]([CH3:36])[N:33]=[C:99]([CH:7]([CH3:6])[CH3:2])[CH:95]=3)=[N:25][N:24]=2)=[CH:20][C:19]=1[CH2:29][CH3:30])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

9

Reactant 6

HCID 5922Isonicotinic AcidHCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 87949Lawesson's reagentHCID 2724699PyBOPHCID 592020264-Benzyloxy-3-ethyl-5-methyl-benzoic acid hydrazide

Product 1

HCID 68554551HCID 68554551, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of isonicotinic acid 13 (900 mg, 4.73 mmol), 4-benzyloxy-3-ethyl-5-methyl-benzoic acid hydrazide (2848 mg, 5.00 mmol) and DIPEA (1.73 g, 13.4 mmol) in DCM (50 mL), PyBOP (3257 mg, 6.26 mmol) is added at 0° C. The mixture is stirred at 0° C. for 30 min before it is diluted with EA, washed with sat. aq. NaHCO3-solution. The org. extract is dried over Na2SO4, filtered and concentrated to give the crude di-acylhydrazide; LC-MS: tR=0.74 min, [M+1]+=446.09. This material and Lawesson reagent (1.86 g, 4.59 mmol) are dissolved in THF (15 mL) and the mixture is heated in the microwave at 110° C. for 5 min. The mixture is diluted with EA, washed with sat. aq. Na2CO3 solution, dried over MgSO4, filtered and concentrated. The crude product is purified by CC on silica gel eluting with heptane:EA 9:1 to give 4-[5-(4-benzyloxy-3-ethyl-5-methyl-phenyl)-[1,3,4]thiadiazol-2-yl]-2-isopropyl-6-methyl-pyridine (837 mg) as a yellow oil; LC-MS: tR=1.00 min, [M+1]+=444.23.

Workup

  1. washwashed with sat. aq. NaHCO3-solution
  2. extractionextract
  3. dry with materialis dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto give the crude di-acylhydrazide
  7. temperaturethe mixture is heated in the microwave at 110° C. for 5 min
  8. washwashed with sat. aq. Na2CO3 solution
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe crude product is purified by CC on silica gel eluting with heptane:EA 9:1

Sources & evidence

ORD record
ord-0867ed7b247d47a1a6c48e7f9040acb7
Source dataset
uspto-grants-2013_11
Patent number
US08580824B2

Reaction notes

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