1,1'-Carbonyldiimidazole → HCID 178461209, compound

HRID 1852779Notes

Reaction equation

HRID 1852779 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:24][C@H:25]4[CH2:30][CH2:29][C@H:28]([CH3:31])[CH2:27][CH2:26]4)[C:15]([N:17]4[CH2:21][CH2:20][CH2:19][C@H:18]4[CH2:22][F:23])=[N:16][C:12]=3[CH:11]=[C:10]([C:32](=[N:34][OH:35])[NH2:33])[N:9]=2)[CH:5]=[N:6][CH:7]=1.[C:36](N1C=CN=C1)(N1C=CN=C1)=[O:37].N12CCCN=C1CCCCC2>C(#N)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[C:13]3[N:14]([CH2:24][C@H:25]4[CH2:30][CH2:29][C@H:28]([CH3:31])[CH2:27][CH2:26]4)[C:15]([N:17]4[CH2:21][CH2:20][CH2:19][C@H:18]4[CH2:22][F:23])=[N:16][C:12]=3[CH:11]=[C:10]([C:32]3[NH:33][C:36](=[O:37])[O:35][N:34]=3)[N:9]=2)[CH:5]=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 178461211HCID 178461211, compound

Product 1

HCID 178461209HCID 178461209, compound

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-(5-chloropyridin-3-yl)-2-[(2S)-2-(fluoromethyl)pyrrolidi n-1-yl]-N′-hydroxy-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridine-6-carboximidamide (408 mg, 0.82 mmol) and 1,1′-carbonyldiimidazole (146 mg, 0.90 mmol) dissolved in acetonitrile (8.2 mL) was added 1,8-diazabicyclo[5.4.0]undec-7-ene (0.488 mL, 3.26 mmol). The reaction mixture was stirred at room temperature for 1 hour. The reaction was washed with water and extracted with dichloromethane. The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient) to afford 3-{4-(5-chloropyridin-3-yl)-2-[(2S)-2-(fluoromethyl)pyrrolidin-1-yl]-3-[(trans-4-methylcyclohexyl)methyl]-3H-imidazo[4,5-c]pyridin-6-yl}-1,2,4-oxadiazol-5(4H)-one. MS ESI calc'd. for C26H29ClFN7O2 [M+H]+ 526. found 526. 1H NMR (500 MHz, DMSO-d6) δ 12.83 (s, 1H), 8.93 (s, 1H), 8.78 (s, 1H), 8.48 (s, 1H), 7.83 (s, 1H), 4.67-4.42 (m, 3H), 3.91-3.81 (m, 1H), 3.79-3.64 (m, 2H), 3.53-3.45 (m, 1H), 2.20-2.12 (broad, 1H), 2.06-1.98 (broad, 1H), 1.94-1.78 (m, 2H), 1.40-1.31 (broad, 2H), 1.17-1.07 (broad, 1H), 1.06-0.96 (broad, 1H), 0.89 (d, J=12.5, 1H), 0.67 (d, J=6.4, 3H), 0.63-0.36 (m, 5H).

Workup

  1. washThe reaction was washed with water
  2. extractionextracted with dichloromethane
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel chromatography (0-100% ethyl acetate/hexanes, linear gradient)

Sources & evidence

ORD record
ord-5ec00a5de9844478b15ebad0adcce073
Source dataset
uspto-grants-2015_02
Patent number
US08962611B2

Reaction notes

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