1,1'-Carbonyldiimidazole → HCID 136078666, compound

HRID 1627904Notes

Reaction equation

HRID 1627904 reaction equation
[CH3:1][C:2]1[N:7]=[C:6]2[S:8][C:9]3[CH2:13][CH:12]([CH3:14])[CH2:11][C:10]=3[C:5]2=[C:4]([C:15]2[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=2)[C:3]=1[CH:22]([CH2:25][CH2:26][CH3:27])[C:23]#[N:24].Cl.NO.[C:31](=[O:34])(O)[O-:32].[Na+].C1N=C[N:38](C(N2C=NC=C2)=O)C=1>CO.O1CCOCC1>[CH3:1][C:2]1[N:7]=[C:6]2[S:8][C:9]3[CH2:13][CH:12]([CH3:14])[CH2:11][C:10]=3[C:5]2=[C:4]([C:15]2[CH:16]=[CH:17][C:18]([CH3:21])=[CH:19][CH:20]=2)[C:3]=1[CH:22]([C:23]1[NH:38][C:31](=[O:34])[O:32][N:24]=1)[CH2:25][CH2:26][CH3:27]

Participants

7

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 443297Hydroxyamine hydrochlorideHCID 516892Sodium BicarbonateHCID 66603864HCID 66603864, compound

Product 1

HCID 136078666HCID 136078666, compoundYield 25%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
65 °C

Procedure

A solution of 2-[2-methyl-6-methyl-4-p-tolyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-b]pyridin-3-yl]pentanenitrile (0.082 g; 0.219 mmol) in methanol (1 mL) was treated with hydroxylamine hydrochloride (0.023 g; 0.331 mmol) and sodium bicarbonate (0.026 mg; 0.310 mmol) and the mixture was heated at 65° C. for 18 h. The volatiles were evaporated and the residue was dissolved in ethyl acetate, washed with brine, dried over magnesium sulphate, filtered and concentrated under reduced pressure to afford the crude N′-hydroxy-2-[2-methyl-6-methyl-4-p-tolyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-b]pyridin-3-yl]pentanimidamide which was mixed with carbodiimidazole (0.050 g; 0.308 mmol) in dioxane (2 mL) and heated at 100° C. for 45 min. The volatiles were removed under reduced pressure and the residue was dissolved in ethyl acetate, washed with brine, dried over magnesium sulphate, filtered and concentrated under reduced pressure. Purification by preparative HPLC (HPLC method 1) furnished 0.023 g (25%) of the title compound as a white solid.

Workup

  1. customThe volatiles were evaporated
  2. dissolutionthe residue was dissolved in ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over magnesium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto afford the crude N′-hydroxy-2-[2-methyl-6-methyl-4-p-tolyl-6,7-dihydro-5H-cyclopenta[4,5]thieno[2,3-b]pyridin-3-yl]pentanimidamide which
  8. temperatureheated at 100° C. for 45 min
  9. customThe volatiles were removed under reduced pressure
  10. dissolutionthe residue was dissolved in ethyl acetate
  11. washwashed with brine
  12. dry with materialdried over magnesium sulphate
  13. filtrationfiltered
  14. concentrationconcentrated under reduced pressure
  15. customPurification by preparative HPLC (HPLC method 1)

Sources & evidence

ORD record
ord-99da5a4f34444b19b903b178cfb0794e
Source dataset
uspto-grants-2014_07
Patent number
US08785638B2

Reaction notes

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