Bis-(1H-imidazol-2-YL)-methanone → Tert-butyl 4-(phenylthio)-3-({3-[4-(pyridin-2-ylamino)butyl]-1,2,4-oxadiazol-5-yl}methyl)butanoate

HRID 1243532Notes

Reaction equation

HRID 1243532 reaction equation
[C:1]([O:5][C:6](=[O:21])[CH2:7][CH:8]([CH2:13][S:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:9][C:10]([OH:12])=O)([CH3:4])([CH3:3])[CH3:2].O[N:23]=[C:24]([NH2:36])[CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=1.C(C1NC=CN=1)(C1NC=CN=1)=O>CN(C=O)C.C(=O)(O)[O-].[Na+]>[C:15]1([S:14][CH2:13][CH:8]([CH2:9][C:10]2[O:12][N:23]=[C:24]([CH2:25][CH2:26][CH2:27][CH2:28][NH:29][C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][N:31]=3)[N:36]=2)[CH2:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:21])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 3

HCID 5250894Bis-(1H-imidazol-2-YL)-methanone2×HCID 219278795-tert-butoxy-5-oxo-3-[(phenylthio)methyl]pentanoic AcidHCID 73853503CID 738535032×

Product 1

HCID 21927896Tert-butyl 4-(phenylthio)-3-({3-[4-(pyridin-2-ylamino)butyl]-1,2,4-oxadiazol-5-yl}methyl)butanoateYield 60%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

The product from step 2 (54 mg, 0.175 mmoles), N′-hydroxy-5-(pyridin-2-ylamino)pentanimidamide (40 mg, 0.192 mmoles) and carbonyl diimidazole (45 mg, 0.28 mmoles) were combined in DMF 1.5 mL and stirred at RT for 4 h then heated at 65° C. overnight. N′-hydroxy-5-(pyridin-2-ylamino)pentanimidamide (36 mg 0.175 mmoles) and carbonyl diimidazole (50 mg, 0.31 mmoles) were added in and reaction was stirred at RT for 2 h follwed by heating to 80° C. for 24 h. Reaction was cooled, diluted with a sodium bicarbonate solution (6 ml, 1:1 saturated bicarbonate solution and water) and extracted with ethyl acetate 3×3 mL. The combined organics were washed with water 2×3 mL, brine 3 mL, dried and passed through a pad of silica eluting with a further 10 mL of ethyl acetate. The solvent was removed under reduced pressure to give the product 50.4 mg (60%). MS (ESI+) for C26H34N4O3S m/z 483 (M+H)+.

Workup

  1. temperaturethen heated at 65° C. overnight
  2. customreaction
  3. stirringwas stirred at RT for 2 h
  4. temperatureby heating to 80° C. for 24 h
  5. customReaction
  6. temperaturewas cooled
  7. extractionextracted with ethyl acetate 3×3 mL
  8. washThe combined organics were washed with water 2×3 mL, brine 3 mL
  9. customdried
  10. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-9ba10dd0a0914f9987ff3284d522719f
Source dataset
uspto-grants-2006_10
Patent number
US07119098B2

Reaction notes

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