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 1425284Notes

Reaction equation

HRID 1425284 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.

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-3f4d6acbc0a240b288e491546a274f78
Source dataset
uspto-grants-2015_01
Patent number
US08927588B2

Reaction notes

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