Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-4-formyl-1,3-thiazole-5-carboxylate → HCID 86648472, compound

HRID 1424922Notes

Reaction equation

HRID 1424922 reaction equation
[CH2:1]([Li])CCC.[Cl:6][C:7]1[N:8]=[C:9]([C:14]([NH:16][C@H:17]2[CH2:22][CH2:21][N:20]([C:23]3[S:24][C:25]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:26]([CH:28]=O)[N:27]=3)[CH2:19][C@H:18]2[O:35][CH3:36])=[O:15])[NH:10][C:11]=1[CH2:12][CH3:13]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1.[Cl-].[Na+].O>[Cl:6][C:7]1[N:8]=[C:9]([C:14]([NH:16][C@H:17]2[CH2:22][CH2:21][N:20]([C:23]3[S:24][C:25]([C:30]([O:32][CH2:33][CH3:34])=[O:31])=[C:26]([CH:28]=[CH2:1])[N:27]=3)[CH2:19][C@H:18]2[O:35][CH3:36])=[O:15])[NH:10][C:11]=1[CH2:12][CH3:13]

Participants

6

Reactant 2

HCID 86648470Ethyl cis(+/-)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-4-formyl-1,3-thiazole-5-carboxylateHCID 178418339Butyllithium

Product 1

HCID 86648472HCID 86648472, compoundYield 21%

Reagents, catalysts & solvents 3

HCID 74505Methyltriphenyliphosphonium bromideCatalystHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-78 °C

Procedure

Methyltriphenylphosphonium bromide (0.19 g, 0.53 mmol) was suspended in THF (4 mL), followed by cooling to −78° C. An n-butyllithium/1.58 M hexane solution (0.34 mL, 0.54 mmol) was added dropwise, followed by stirring for 25 minutes. Ethyl cis(±)-2-(4-{[(4-chloro-5-ethyl-1H-imidazol-2-yl)carbonyl]amino}-3-methoxypiperidin-1-yl)-4-formyl-1,3-thiazole-5-carboxylate obtained in Example (28a) (74 mg, 0.16 mmol) was added, and the mixture was heated to room temperature and stirred for one hour. Brine was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. Following concentration under reduced pressure, the residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=4/1, 3/1, 1/1) to obtain 15 mg of the title compound as a pale yellow solid (21%).

Workup

  1. temperaturethe mixture was heated to room temperature
  2. stirringstirred for one hour
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentration under reduced pressure
  7. customthe residue was purified by silica gel column chromatography (elution solvent: hexane/ethyl acetate=4/1, 3/1, 1/1)

Sources & evidence

ORD record
ord-72393f5567944fdba13c67b1a1b13115
Source dataset
uspto-grants-2015_01
Patent number
US08927588B2

Reaction notes

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