Acetic Acid → HCID 178447712, compound

HRID 1852885Notes

Reaction equation

HRID 1852885 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:22][C@H:23]4[CH2:28][CH2:27][C@H:26]([CH3:29])[CH2:25][CH2:24]4)[C:15]([C:17]([CH:19]([CH3:21])[CH3:20])=[CH2:18])=[N:16][C:12]=3[CH:11]=[C:10]([C:30]3[NH:34][C:33](=[O:35])[O:32][N:31]=3)[N:9]=2)[CH:5]=[N:6][CH:7]=1.[CH3:36][S:37]([O-:39])=[O:38].[Na+].C(O)(=O)C>C(O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:22][C@H:23]4[CH2:28][CH2:27][C@H:26]([CH3:29])[CH2:25][CH2:24]4)[C:15]([CH:17]([CH2:18][S:37]([CH3:36])(=[O:39])=[O:38])[CH:19]([CH3:20])[CH3:21])=[N:16][C:12]=3[CH:11]=[C:10]([C:30]3[NH:34][C:33](=[O:35])[O:32][N:31]=3)[N:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 2733271Sodium methanesulfinateHCID 178437399HCID 178437399, compound

Product 1

HCID 178447712HCID 178447712, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

To a stirred solution of 3-{4-(5-chloropyridin-3-yl)-2-(3-methylbut-1-en-2-yl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridin-6-yl}-1,2,4-oxadiazol-5(4H)-one (synthesized in a manner similar to Example 9.1; 20 mg, 0.046 mmol) in dry ethanol (0.7 mL) was added sodium methanesulfinate (47 mg, 0.46 mmol) followed by acetic acid (27 μL, 0.046 mmol). The reaction mixture was heated to 60° C. for 12 h. The reaction mixture was then cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in ethyl acetate and washed with water and brine. The organic layer was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The residue obtained was purified by reverse phase prep-HPLC (Kromasil C18, water/MeOH+0.1% TFA) to give 3-[4-(5-chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-{2-methyl-1-[(methylsulfonyl)methyl]propyl}-3H-imidazo[4,5-c]pyridin-6-yl]-1,2,4-oxadiazol-5(4H)-one (TFA salt, racemate). 1H NMR (400 MHz, DMSO-d6): δ 12.90 (br s, 1H), 8.86 (s, 1H), 8.85 (s, 1H), δ 8.43 (s, 1H), 8.24 (s, 1H), 4.07-3.96 (m, 2H), 3.84-3.79 (m, 1H), 3.67-3.64 (m, 2H), 3.02 (s, 3H), 2.21-2.16 (m, 1H), 1.39 (d, J=11.6 Hz, 2H), 1.22-1.15 (m, 2H), 1.04 (d, J=6.7 Hz, 3H), 0.83 (d, J=6.7 Hz, 3H), 0.70 (d, J=6.5 Hz, 3H), 0.78-0.41 (m, 6H). MS ES/APCI calc'd. for C27H33ClN6O4S [M+H]+ 573. found 573.

Workup

  1. temperatureThe reaction mixture was then cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed with water and brine
  5. dry with materialThe organic layer was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue obtained
  9. customwas purified by reverse phase prep-HPLC (Kromasil C18, water/MeOH+0.1% TFA)

Sources & evidence

ORD record
ord-838c4c84fe874e3881d826d71c995509
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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