Diisopropylethylamine → Methyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-1,3-benzoxazole-7-carboxylate

HRID 43820Notes

Reaction equation

HRID 43820 reaction equation
Cl.C(OCC)(=O)C.[Cl:8][C:9]1[N:10]=[C:11]([C:16]([NH:18][C@H:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27]C(C)(C)C)=O)[CH2:21][C@H:20]2[O:32][CH3:33])=[O:17])[NH:12][C:13]=1[CH2:14][CH3:15].ClC1O[C:37]2[C:43]([C:44]([O:46][CH3:47])=[O:45])=[CH:42][CH:41]=[CH:40][C:38]=2[N:39]=1.C(N(C(C)C)CC)(C)C>C(OCC)(=O)C.CO>[Cl:8][C:9]1[N:10]=[C:11]([C:16]([NH:18][C@H:19]2[CH2:24][CH2:23][N:22]([C:25]3[O:27][C:37]4[C:43]([C:44]([O:46][CH3:47])=[O:45])=[CH:42][CH:41]=[CH:40][C:38]=4[N:39]=3)[CH2:21][C@H:20]2[O:32][CH3:33])=[O:17])[NH:12][C:13]=1[CH2:14][CH3:15]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 21866389Hydrogen chloride-ethyl acetateHCID 68406054Methyl 2-chloro-1,3-benzoxazole-7-carboxylateHCID 86648452tert-Butyl cis(+/-)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidine-1-carboxylate

Product 1

HCID 86648764Methyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-1,3-benzoxazole-7-carboxylateYield 101.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methanol (2 ml) and a 4 N hydrochloric acid/ethyl acetate solution (2 mL) were added to tert-butyl cis(±)-4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidine-1-carboxylate obtained in Example (1g) (60 mg, 0.16 mmol), and the mixture was stirred at room temperature for two hours. Following concentration under reduced pressure, the residue was dissolved in DMF (4 mL). Methyl 2-chloro-1,3-benzooxazole-7-carboxylate (34 mg, 0.16 mmol) (reference: U.S. Pat. No. 6,166,011 A1) and diisopropylethylamine (1 ml) were added, and the mixture was stirred at 80° C. for six hours. Ethyl acetate was added to the reaction solution, and the organic layer was washed with water and dried over anhydrous sodium sulfate. Following concentration under reduced pressure, the residue was recrystallized from an ethyl acetate/hexane solvent to obtain 75 mg of the title compound as crystals. mass spectrum (ESI): m/z 462 (M+H)+.

Workup

  1. concentrationconcentration under reduced pressure
  2. dissolutionthe residue was dissolved in DMF (4 mL)
  3. stirringthe mixture was stirred at 80° C. for six hours
  4. washthe organic layer was washed with water
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentration under reduced pressure
  7. customthe residue was recrystallized from an ethyl acetate/hexane solvent

Sources & evidence

ORD record
ord-2eeb99f39a9243358d47d1b8c1695b46
Source dataset
uspto-grants-2013_09
Patent number
US08536197B2

Reaction notes

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