HCID 70558848, compound → HCID 86702023, compound

HRID 2278801Notes

Reaction equation

HRID 2278801 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:18]2[N:22]=[C:21]([C:23]3[CH:28]=[C:27]([O:29][CH3:30])[N:26]=[C:25]([CH:31]4[CH2:35][CH2:34][CH2:33][CH2:32]4)[CH:24]=3)[O:20][N:19]=2)[CH:5]=[C:6]([CH3:17])[C:7]=1[O:8][CH2:9][CH:10](OCC)[O:11]CC>O1CCOCC1.OS(O)(=O)=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:18]2[N:22]=[C:21]([C:23]3[CH:28]=[C:27]([O:29][CH3:30])[N:26]=[C:25]([CH:31]4[CH2:35][CH2:34][CH2:33][CH2:32]4)[CH:24]=3)[O:20][N:19]=2)[CH:5]=[C:6]([CH3:17])[C:7]=1[O:8][CH2:9][CH:10]=[O:11]

Participants

4

Reactant 1

HCID 70558848HCID 70558848, compound

Product 1

HCID 86702023HCID 86702023, compoundYield 118.6%

Reagents, catalysts & solvents 2

HCID 1118Sulfuric AcidSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 3-(3-chloro-4-(2,2-diethoxyethoxy)-5-methylphenyl)-5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazole (1.01 g, 2.01 mmol) in dioxane (15 mL) and 2 M aq. H2SO4 (5 mL) is stirred at 80° C. for 3 h. The mixture is extracted with EA (100 mL) and the org. extract is washed twice with brine (2×35 mL), dried over MgSO4, filtered and concentrated to give crude 2-(2-chloro-4-(5-(2-cyclopentyl-6-methoxypyridin-4-yl)-1,2,4-oxadiazol-3-yl)-6-methylphenoxy)acetaldehyde (1.02 g) as a yellow oil; LC-MS: tR=1.11 min, [M+H]+=428.19. Part of this material (345 mg, 0.806 mmol.) is dissolved in DCM (10 mL), methanol (10 mL) and acetic acid (0.7 ml) before β-alanine (72 mg, 0.806 mmol) is added. The mixture is degassed and put under argon before Na(BH3CN) (23 mg, 0.364 mmol) is added. The clear solution is stirred at rt for 2 h before the reaction is quenched by adding water (2 mL). The mixture is concentrated and the crude product is purified by prep. HPLC to give the title compound (77 mg) as a brownish solid; LC-MS: tR=0.95 min, [M+H]+=501.23; 1H NMR (CDCl3): δ 8.53 (s br, 2H), 7.83 (s, 1H), 7.67 (s, 1H), 7.33 (s, 1H), 7.07 (s, 1H), 4.20-4.30 (m, 2H), 3.95 (s, 3H), 3.39-3.49 (m, 2H), 3.25-3.36 (m, 2H), 3.12-3.22 (m, 1H), 2.64-2.75 (m, 2H), 2.32 (s, 3H), 2.02-2.12 (m, 2H), 1.78-1.91 (m, 4H), 1.68-1.78 (m, 2H).

Workup

  1. extractionThe mixture is extracted with EA (100 mL)
  2. extractionextract
  3. washis washed twice with brine (2×35 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-a4ddfeadc7b042e3869c343169f48390
Source dataset
uspto-grants-2015_09
Patent number
US09133179B2

Reaction notes

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