1,2-Dichloroethane → (R)-5-tert-butyl-N-(1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethyl)isoxazole-3-carboxamide

HRID 511856

반응식

HRID 511856 반응식
Cl.Cl.[F:3][C:4]([F:17])([F:16])[CH2:5][O:6][C:7]1[CH:8]=[CH:9][C:10]([C@H:13]([NH2:15])[CH3:14])=[N:11][CH:12]=1.[C:18]([C:22]1[O:26][N:25]=[C:24]([C:27](O)=[O:28])[CH:23]=1)([CH3:21])([CH3:20])[CH3:19].C(N(CC)CC)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1>ClCCl.CO>[C:18]([C:22]1[O:26][N:25]=[C:24]([C:27]([NH:15][C@@H:13]([C:10]2[CH:9]=[CH:8][C:7]([O:6][CH2:5][C:4]([F:3])([F:16])[F:17])=[CH:12][N:11]=2)[CH3:14])=[O:28])[CH:23]=1)([CH3:21])([CH3:19])[CH3:20]

참가 물질

8

반응물 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 173896645-tert-Butyl-1,2-oxazole-3-carboxylic acidHCID 66892447(1R)-1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethan-1-amine dihydrochloride

생성물 1

HCID 67289670(R)-5-tert-butyl-N-(1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethyl)isoxazole-3-carboxamide수율 75%

시약·촉매·용매 2

HCID 887Methanol용매HCID 6344Dichloromethane용매

실험 절차

To a suspension of (R)-1-(5-(2,2,2-trifluoroethoxy)pyridin-2-yl)ethanamine 2HCl salt (18 mg, 0.06 mmol) and 5-tert-butylisoxazole-3-carboxylic acid (10 mg, 0.06 mmol) in dichloromethane (2 mL) were added triethylamine (19 mg, 0.18 mmol), EDC (19 mg, 0.1 mmol) and HOBT (9.4 mg, 0.06 mmol) respectively. The reaction mixture was stirred at room temperature for 18 hours. The solvent was evaporated by N2-flow. The resulting residue was dissolved into ethyl acetate and water was added to the mixture. The organic layer was then washed with brine, and dried over sodium sulfate. After the filtration to separate solvent and sodium sulfate, the solvent was removed under reduced pressure to give the residue. The residue was diluted with methanol and applied onto a strong cation exchange cartridge (BondElute(registered trademark) SCX, 1 g/6 mL, Varian Inc.), and the solid phase matrix was rinsed with methanol (6 mL). The crude mixture was eluted in a collection tube with 1 mol/L ammonia in methanol (6 mL) and concentrated in vacuo. The residue was purified by preparative LC-MS to give 17 mg, (75% yield) of the title compound.

후처리

  1. customThe solvent was evaporated by N2-flow
  2. dissolutionThe resulting residue was dissolved into ethyl acetate and water
  3. additionwas added to the mixture
  4. washThe organic layer was then washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationAfter the filtration
  7. customto separate solvent and sodium sulfate
  8. customthe solvent was removed under reduced pressure
  9. customto give the residue
  10. wash), and the solid phase matrix was rinsed with methanol (6 mL)
  11. washThe crude mixture was eluted in a collection tube with 1 mol/L ammonia in methanol (6 mL)
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by preparative LC-MS

출처 및 근거

ORD 기록
ord-8bb666ab618f4b7ba810fee4684aeaf2
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09101616B2

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