1-Hydroxybenzotriazole → N-(2-Chloro-4-{5-[2-(1-ethyl-propyl)-6-methoxy-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenyl)-methanesulfonamide

HRID 245109Notes

Reaction equation

HRID 245109 reaction equation
C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[CH2:23]([CH:25]([C:28]1[CH:29]=[C:30]([CH:34]=[C:35]([O:37][CH3:38])[N:36]=1)[C:31]([OH:33])=O)[CH2:26][CH3:27])[CH3:24].[Cl:39][C:40]1[CH:41]=[C:42]([CH:47]=[C:48]([CH3:55])[C:49]=1[NH:50][S:51]([CH3:54])(=[O:53])=[O:52])[C:43]([NH:45]O)=[NH:44]>CN(C=O)C.C([O-])(O)=O.[Na+]>[Cl:39][C:40]1[CH:41]=[C:42]([C:43]2[N:45]=[C:31]([C:30]3[CH:34]=[C:35]([O:37][CH3:38])[N:36]=[C:28]([CH:25]([CH2:23][CH3:24])[CH2:26][CH3:27])[CH:29]=3)[O:33][N:44]=2)[CH:47]=[C:48]([CH3:55])[C:49]=1[NH:50][S:51]([CH3:54])(=[O:53])=[O:52]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 584181082-(1-Ethylpropyl)-6-methoxyisonicotinic acidHCID 178426664HCID 178426664, compound

Product 1

HCID 49872068N-(2-Chloro-4-{5-[2-(1-ethyl-propyl)-6-methoxy-pyridin-4-yl]-[1,2,4]oxadiazol-3-yl}-6-methyl-phenyl)-methanesulfonamideYield 57.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

HOBt (20 mg, 148 μmol) and EDC HCl (28 mg, 148 μmol) are added to a solution of 2-(1-ethyl-propyl)-6-methoxy-isonicotinic acid (30 mg, 134 μmol) in DMF (5 mL). The mixture is stirred at rt for 5 min before 3-chloro-N-hydroxy-4-methanesulfonylamino-5-methyl-benzamidine (38 mg, 136 μmol) is added. The mixture is stirred at rt for 18 h before it is diluted with sat. aq. NaHCO3 solution and extracted twice with EA. The combined org. extracts are dried over MgSO4, filtered and concentrated. The resulting orange oil (65 mg) is dissolved in dioxane (5 mL) and heated to 80° C. for 3 h. The solvent is removed in vacuo and the crude product is purified on prep. TLC plates using heptane:EA 3:2 to give the title compound (36 mg) as a white solid; LC-MS**: tR=0.88 min, [M+H]+=465.06; 1H NMR (CDCl3): δ0.84 (t, J=7.5 Hz, 6H), 1.69-1.88 (m, 4H), 2.56-2.63 (m, 1H), 2.65 (s, 3H), 3.17 (s, 3H), 4.02 (s, 3H), 6.26 (s, 1H), 7.32 (d, J=1.0 Hz, 1H), 7.43 (d, J=0.8 Hz, 1H), 8.07 (d, J=1.0 Hz, 1H), 8.17 (d, J=1.5 Hz, 1H).

Workup

  1. additionis added
  2. extractionextracted twice with EA
  3. dry with materialextracts are dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe resulting orange oil (65 mg) is dissolved in dioxane (5 mL)
  7. temperatureheated to 80° C. for 3 h
  8. customThe solvent is removed in vacuo
  9. customthe crude product is purified on prep

Sources & evidence

ORD record
ord-f0105de700774002b4f0d19a89dcb3d6
Source dataset
uspto-grants-2014_02
Patent number
US08658675B2

Reaction notes

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