Hydrochloric Acid → HCID 67197427, compound

HRID 1807618Notes

Reaction equation

HRID 1807618 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C:13]2[O:17][N:16]=[C:15]([C:18]3[CH:19]=[C:20]4[C:24](=[CH:25][CH:26]=3)[N:23](C(OC(C)(C)C)=O)[CH:22]=[CH:21]4)[N:14]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH:10]([CH3:12])[CH3:11])#[N:2].O1CCOCC1.Cl.Cl.O1CCOCC1>CCOC(C)=O>[NH:23]1[C:24]2[C:20](=[CH:19][C:18]([C:15]3[N:14]=[C:13]([C:5]4[CH:6]=[CH:7][C:8]([O:9][CH:10]([CH3:12])[CH3:11])=[C:3]([CH:4]=4)[C:1]#[N:2])[O:17][N:16]=3)=[CH:26][CH:25]=2)[CH:21]=[CH:22]1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-Dioxane2×HCID 204431481,4-Dioxane hydrochlorideHCID 67198701HCID 67198701, compound

Product 1

HCID 67197427HCID 67197427, compoundYield 30%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a flask containing tert-butyl 5-(5-(3-cyano-4-isopropoxyphenyl)-1,2,4-oxadiazol-3-yl)-1H-indole-1-carboxylate INT-67 (75 mg, 0.17 mmol) was added dioxane (2 mL) followed by 4N HCl in dioxane (0.5 mL, 2 mmol). The reaction mixture was stirred overnight at room temperature then heated at 50° C. overnight. Additional 4N HCl/dioxane (0.5 mL, 2 mmol) was added and the mixture was heated at 50° C. for an additional 2 h to complete the deprotection. The reaction mixture was diluted with EtOAc and washed with NaHCO3. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated. The material was purified by chromatography (EtOAc/hexanes) to provide 17 mg (30%) of 5-(3-(1H-indol-5-yl)-1,2,4-oxadiazol-5-yl)-2-isopropoxybenzonitrile 68 as a white solid. LCMS-ESI (m/z) calculated for C20H16N4O2: 344.5; found 345.1 [M+H]+, tR=2.34 min (Method 1). 1H NMR (400 MHz, CDCl3) δ 8.51-8.47 (m, 1H), 8.45 (d, J=2.2 Hz, 1H), 8.38 (d, J=7.2 Hz, 1H), 8.35 (dd, J=8.9, 2.2 Hz, 1H), 7.99 (dd, J=8.5, 1.6 Hz, 1H), 7.51 (d, J=8.5 Hz, 1H), 7.33-7.28 (m, 1H), 7.11 (d, J=9.0 Hz, 1H), 6.72-6.64 (m, 1H), 4.79 (dt, J=12.2, 6.1 Hz, 1H), 1.47 (t, J=5.8 Hz, 6H).

Workup

  1. temperaturethen heated at 50° C. overnight
  2. temperaturethe mixture was heated at 50° C. for an additional 2 h
  3. washwashed with NaHCO3
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customThe material was purified by chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-e3218e42ac544003a4bee95255d69921
Source dataset
uspto-grants-2013_01
Patent number
US08357706B2

Reaction notes

Loading…