Phenylacetyl chloride → Pyrrolidine-1-carboxylic acid {4-[3-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyridin-2-yl}amide

HRID 492782노트

반응식

HRID 492782 반응식
[C:1]1([CH2:7][C:8](Cl)=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[S-:11][C:12]#[N:13].[K+].[NH2:15][C:16]1[CH:36]=[CH:35][C:19]([O:20][C:21]2[CH:26]=[CH:25][N:24]=[C:23]([NH:27][C:28]([N:30]3[CH2:34][CH2:33][CH2:32][CH2:31]3)=[O:29])[CH:22]=2)=[CH:18][C:17]=1[F:37]>C(#N)C.C(OCC)C>[F:37][C:17]1[CH:18]=[C:19]([CH:35]=[CH:36][C:16]=1[NH:15][C:12]([NH:13][C:8](=[O:9])[CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[S:11])[O:20][C:21]1[CH:26]=[CH:25][N:24]=[C:23]([NH:27][C:28]([N:30]2[CH2:34][CH2:33][CH2:32][CH2:31]2)=[O:29])[CH:22]=1

참가 물질

6

반응물 3

HCID 7679Phenylacetyl chlorideHCID 516872Potassium thiocyanateHCID 57677638N-[4-(4-Amino-3-fluorophenoxy)-2-pyridinyl]-1-pyrrolidinecarboxamide

생성물 1

HCID 57677648Pyrrolidine-1-carboxylic acid {4-[3-fluoro-4-(3-phenylacetylthioureido)phenoxy]pyridin-2-yl}amide수율 13%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 6342Acetonitrile용매2회

반응 조건

온도
60 °C

실험 절차

To a solution of 2-phenylacetyl chloride (0.054 ml, 0.43 mmol) in acetonitrile (4.3 ml) was added potassium thiocyanate (83 mg) at room temperature, followed by stirring under a nitrogen atmosphere at 60° C. for 1.5 hrs. The reaction mixture was cooled in an ice bath, and then a solution of pyrrolidine-1-carboxylic acid [4-(4-amino-3-fluorophenoxy)pyridin-2-yl]amide (90 mg) in acetonitrile (4.0 ml) was added thereto, followed by warming the reaction mixture to room temperature and stirring for 3 hrs. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:1 to 1:2, then ethyl acetate). Fractions containing the target compound were concentrated to give a solid, which was suspended in diethyl ether. The solid was filtered off, washed with diethyl ether, and dried under aeration to provide the titled compound (18 mg, 13%) as colorless powder.

후처리

  1. temperatureThe reaction mixture was cooled in an ice bath
  2. temperatureby warming the reaction mixture to room temperature
  3. stirringstirring for 3 hrs
  4. customThe reaction mixture was partitioned between ethyl acetate and water
  5. washThe organic layer was washed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated
  8. customto give a residue, which
  9. customwas then purified by silica gel column chromatography (eluent
  10. additionFractions containing the target compound
  11. concentrationwere concentrated
  12. customto give a solid, which
  13. filtrationThe solid was filtered off
  14. washwashed with diethyl ether
  15. customdried under aeration

출처 및 근거

ORD 기록
ord-e4f3f547c5244df7a3bb12b8a4625f9f
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07531532B2

반응 노트

불러오는 중…