Sodium Iodide → 1-(((5S,7S)-7-methyl-3-(4-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile

HRID 715549Notes

Reaction equation

HRID 715549 reaction equation
C[O:2][C:3]1[N:8]=[CH:7][C:6]([N:9]2[CH2:13][C@@:12]3([CH2:18][CH2:17][CH2:16][C@@:15]([CH2:20][N:21]4[C:25]5[CH:26]=[C:27]([C:30]#[N:31])[CH:28]=[CH:29][C:24]=5[N:23]=[CH:22]4)([CH3:19])[CH2:14]3)[O:11][C:10]2=[O:32])=[C:5]([CH3:33])[CH:4]=1.[I-].[Na+].C[Si](Cl)(C)C>C(#N)C>[CH3:19][C@:15]1([CH2:20][N:21]2[C:25]3[CH:26]=[C:27]([C:30]#[N:31])[CH:28]=[CH:29][C:24]=3[N:23]=[CH:22]2)[CH2:16][CH2:17][CH2:18][C@:12]2([O:11][C:10](=[O:32])[N:9]([C:6]3[C:5]([CH3:33])=[CH:4][C:3](=[O:2])[NH:8][CH:7]=3)[CH2:13]2)[CH2:14]1

Participants

5

Reactant 3

HCID 5238Sodium Iodide2×HCID 6397Chlorotrimethylsilane2×HCID 71226830HCID 71226830, compound

Product 1

HCID 712277541-(((5S,7S)-7-methyl-3-(4-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a suspension of 1-(((5S,7S)-3-(6-methoxy-4-methylpyridin-3-yl)-7-methyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile (5000 mg, 11.22 mmol) and sodium iodide (5047 mg, 33.7 mmol) in Acetonitrile (42.900 mL) was added TMSCl (4.30 mL, 33.7 mmol). The reaction was stirred at room temperature overnight. More sodium iodide (5047 mg, 33.7 mmol) and TMSCl (4.30 mL, 33.7 mmol) were added and stirred overnight at room temperature. The reaction mixture was concentrated to remove MeCN, and the residue was partitioned between saturated aqueous sodium metabisulfite (30 mL) and 10% MeOH/DCM (50 mL). The layers were separated, and the aqueous layer was extracted with 2×DCM. The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The material was purified by ISCO Rf chromatography (220 g column, silica load): 0-20% MeOH/DCM (20 min), 20% MeOH/DCM (20 min). Obtained 1-(((5S,7S)-7-methyl-3-(4-methyl-6-oxo-1,6-dihydropyridin-3-yl)-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)-1H-benzo[d]imidazole-6-carbonitrile as a white foam (3.35 g, 69%). MS (m/z) 432.2 (M+H+).

Workup

  1. stirringstirred overnight at room temperature
  2. concentrationThe reaction mixture was concentrated
  3. customto remove MeCN
  4. customthe residue was partitioned between saturated aqueous sodium metabisulfite (30 mL) and 10% MeOH/DCM (50 mL)
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with 2×DCM
  7. dry with materialThe combined organic extracts were dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe material was purified by ISCO Rf chromatography (220 g column, silica load)
  11. custom0-20% MeOH/DCM (20 min), 20% MeOH/DCM (20 min)

Sources & evidence

ORD record
ord-4bca04832e534cde9fd070f5af5c992c
Source dataset
uspto-grants-2015_11
Patent number
US09187464B2

Reaction notes

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