Hydrochloric Acid → 2-[(1-Methylethyl)oxy]-5-[3-(1,2,3,4-tetrahydro-5-isoquinolinyl)-1,2,4-oxadiazol-5-yl]benzonitrile

HRID 2383301Notes

Reaction equation

HRID 2383301 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:27]=[CH:26][CH:25]=[C:24]4[C:19]=3[CH2:20][CH2:21][N:22](C(OC(C)(C)C)=O)[CH2:23]4)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].Cl>O1CCOCC1.CO>[CH3:12][CH:10]([O:9][C:8]1[CH:7]=[CH:6][C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:27]=[CH:26][CH:25]=[C:24]4[C:19]=3[CH2:20][CH2:21][NH:22][CH2:23]4)[N:14]=2)=[CH:4][C:3]=1[C:1]#[N:2])[CH3:11]

Participants

5

Reactant 2

HCID 313Hydrochloric AcidHCID 575059191,1-dimethylethyl 5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate

Product 1

HCID 441248992-[(1-Methylethyl)oxy]-5-[3-(1,2,3,4-tetrahydro-5-isoquinolinyl)-1,2,4-oxadiazol-5-yl]benzonitrile

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 1,1-dimethylethyl 5-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-3,4-dihydro-2(1H)-isoquinolinecarboxylate (Preparation 6, 512 mg, 1.11 mmol) and 4M HCl in dioxane (20 ml) was stirred at room temperature for 18 h. The mixture was concentrated in vacuo to give a pale yellow solid, which was redissolved in MeOH. This solution was applied to an SCX-3 cartridge (10 g), and the product eluted with 1% NH3 in MeOH. Concentration gave a yellow oil, that became a solid on standing overnight (366 mg). 1H NMR (400 MHz, d6-DMSO) δ 8.38 (1H, d), 8.32 (1H, dd), 7.94 (1H, d), 7.32-7.17 (2H, m), 7.13 (1H, m), 4.80 (1H, sept), 4.10 (2H, s), 3.20-3.14 (4H, m), 1.48 (6H, d); m/z (ES) 361 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customto give a pale yellow solid, which
  3. washthe product eluted with 1% NH3 in MeOH
  4. concentrationConcentration
  5. customgave a yellow oil, that
  6. waiton standing overnight

Sources & evidence

ORD record
ord-f854e596eea54f91bbeeadb46233f0f7
Source dataset
uspto-grants-2012_09
Patent number
US08263620B2

Reaction notes

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