Sodium Methoxide → HCID 178494766, compound

HRID 81236Notes

Reaction equation

HRID 81236 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:25][C@H:26]4[CH2:31][CH2:30][C@H:29]([CH3:32])[CH2:28][CH2:27]4)[C:15]([C:17]([C:19]4[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=4)=[CH2:18])=[N:16][C:12]=3[CH:11]=[C:10]([C:33]3[NH:37][C:36](=[O:38])[O:35][N:34]=3)[N:9]=2)[CH:5]=[N:6][CH:7]=1.[CH3:39][O-:40].[Na+]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:25][C@H:26]4[CH2:27][CH2:28][C@H:29]([CH3:32])[CH2:30][CH2:31]4)[C:15]([CH:17]([C:19]4[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=4)[CH2:18][O:40][CH3:39])=[N:16][C:12]=3[CH:11]=[C:10]([C:33]3[NH:37][C:36](=[O:38])[O:35][N:34]=3)[N:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 178435920HCID 178435920, compound

Product 1

HCID 178494766HCID 178494766, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
75 °C

Procedure

3-[4-(5-Chloropyridin-3-yl)-3-[(trans-4-methylcyclohexyl)methyl]-2-(1-phenylethenyl)-3H-imidazo[4,5-c]pyridin-6-yl]-1,2,4-oxadiazol-5(4H)-one (Example 9.1, 130 mg, 0.247 mmol) was taken up in methanol (1.644 mL) at room temperature, and sodium methoxide (1.2 mL of 25 wt % in methanol, 5.25 mmol) was added. The mixture was capped and heated to 75° C. for 24 hours. The mixture was cooled to room temperature, quenched with saturated aqueous ammonium chloride, and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The resulting residue was purified via automated reverse phase HPLC (methanol/water+0.1% TFA modifier) to afford 3-{4-(5-chloropyridin-3-yl)-2-(2-methoxy-1-phenylethyl)-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridin-6-yl}-1,2,4-oxadiazol-5(4H)-one (TFA salt) as a white solid. MS ESI calcd. for C30H31ClN6O3 [M+H]+ 559. found 559. 1H NMR (500 MHz, DMSO-d6) δ 12.91 (s, 1H), 8.83 (s, 2H), 8.40 (s, 1H), 8.32 (s, 1H), 7.58-7.48 (m, 2H), 7.31-7.25 (m, 3H), 4.80-4.75 (m, 1H), 4.21-4.15 (m, 1H), 3.90-3.80 (m, 3H), 3.25 (s, 3H), 1.42-1.35 (m, 1H), 1.29-1.20 (m, 2H), 1.04-0.94 (m, 1H), 0.75-0.64 (m, 5H), 0.40-0.29 (m, 4H).

Workup

  1. customThe mixture was capped
  2. temperatureThe mixture was cooled to room temperature
  3. customquenched with saturated aqueous ammonium chloride
  4. extractionextracted with ethyl acetate
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe resulting residue was purified via automated reverse phase HPLC (methanol/water+0.1% TFA modifier)

Sources & evidence

ORD record
ord-b469d21515344e11ace512bdb408afc2
Source dataset
uspto-grants-2014_09
Patent number
US08846657B2

Reaction notes

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