Diisopropylethylamine → 4-{3-[4-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-ethyl-5-methyl-phenyl]-[1,2,4]oxadiazol-5-yl}-2-(1-ethyl-propyl)-6-methoxy-pyridine

HRID 245100Notes

Reaction equation

HRID 245100 reaction equation
[CH2:1]([CH:3]([C:6]1[CH:7]=[C:8]([CH:12]=[C:13]([O:15][CH3:16])[N:14]=1)[C:9]([OH:11])=O)[CH2:4][CH3:5])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH3:48][C:49]1([CH3:69])[O:53][C@H:52]([CH2:54][O:55][C:56]2[C:65]([CH3:66])=[CH:64][C:59]([C:60]([NH:62]O)=[NH:61])=[CH:58][C:57]=2[CH2:67][CH3:68])[CH2:51][O:50]1>C1COCC1.CN(C=O)C.CC(=O)OCC>[CH3:48][C:49]1([CH3:69])[O:53][C@H:52]([CH2:54][O:55][C:56]2[C:65]([CH3:66])=[CH:64][C:59]([C:60]3[N:62]=[C:9]([C:8]4[CH:12]=[C:13]([O:15][CH3:16])[N:14]=[C:6]([CH:3]([CH2:1][CH3:2])[CH2:4][CH3:5])[CH:7]=4)[O:11][N:61]=3)=[CH:58][C:57]=2[CH2:67][CH3:68])[CH2:51][O:50]1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 584181082-(1-Ethylpropyl)-6-methoxyisonicotinic acidHCID 178436628HCID 178436628, compound

Product 1

HCID 674914894-{3-[4-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-ethyl-5-methyl-phenyl]-[1,2,4]oxadiazol-5-yl}-2-(1-ethyl-propyl)-6-methoxy-pyridineYield 70.6%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(1-ethyl-propyl)-6-methoxy-isonicotinic acid (190 mg, 732 μmol) in THF (10 mL) and DMF (2 mL), DIPEA (190 mg, 1.46 mmol) followed by TBTU (235 mg, 732 μmol) is added. The mixture is stirred at rt for 10 min before (R)-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-ethyl-N-hydroxy-5-methyl-benzamidine 226 mg, 732 μmol) is added. The mixture is stirred at rt for 1 h before it is diluted with EA and washed with water. The org. phase is separated and concentrated. The remaining residue is dissolved in dioxane (10 mL) and heated to 105° C. for 18 h. The mixture is cooled to rt, concentrated and the crude product is purified on prep. TLC plates using DCM containing 10% of methanol to give 4-{3-[4-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-3-ethyl-5-methyl-phenyl]-[1,2,4]oxadiazol-5-yl}-2-(1-ethyl-propyl)-6-methoxy-pyridine (256 mg) as a yellow oil; LC-MS: tR=1.28 min, [M+H]+=496.23.

Workup

  1. additionis added
  2. additionis added
  3. washwashed with water
  4. customphase is separated
  5. concentrationconcentrated
  6. dissolutionThe remaining residue is dissolved in dioxane (10 mL)
  7. temperatureheated to 105° C. for 18 h
  8. temperatureThe mixture is cooled to rt
  9. concentrationconcentrated
  10. customthe crude product is purified on prep

Sources & evidence

ORD record
ord-e039f9faf6f3481d908c4bff18a47a82
Source dataset
uspto-grants-2014_02
Patent number
US08658675B2

Reaction notes

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