Potassium Carbonate → 1-[2-(4-Biphenyl-2-ylmethyl-piperazin-1-yl)-thiazol-4-ylmethyl]-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine

HRID 410345노트

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HRID 410345 반응식
Cl[C:2]1[S:3][CH:4]=[C:5]([CH2:7][N:8]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[N:10]([CH2:17][CH2:18][CH2:19][O:20][C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=3)[C:9]2=[NH:28])[N:6]=1.[C:29]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH2:35][N:36]1[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1.C([O-])([O-])=O.[K+].[K+]>CN1CCCC1=O.[Cu]I>[C:29]1([C:42]2[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=2)[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=1[CH2:35][N:36]1[CH2:37][CH2:38][N:39]([C:2]2[S:3][CH:4]=[C:5]([CH2:7][N:8]3[C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=4[N:10]([CH2:17][CH2:18][CH2:19][O:20][C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[C:9]3=[NH:28])[N:6]=2)[CH2:40][CH2:41]1

참가 물질

6

반응물 3

HCID 11430Potassium CarbonateHCID 183819371-Biphenyl-2-ylmethyl-piperazineHCID 585649551-(2-Chloro-thiazol-4-ylmethyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine

생성물 1

HCID 462404721-[2-(4-Biphenyl-2-ylmethyl-piperazin-1-yl)-thiazol-4-ylmethyl]-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine수율 8%

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 13387N-methyl-2-pyrrolidone용매

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온도
190 °C

실험 절차

To a solution of 1-(2-chloro-thiazol-4-ylmethyl)-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine (30 mg, 0.072 mmol) in N-methylpyrrolidinone (2 ml) was added 1-biphenyl-2-ylmethyl-piperazine (18 mg, 0.072 mmol), CuI (14 mg, 0.072 mmol) and K2CO3 (15 mg, 0.11 mmol). The reaction was heated in a microwave at 190° C. for a total of 1.5 h. After this time, the suspension was cooled to rt and filtered through Celite®. The collected solids were washed with dichloromethane and then the combined filtrate and washings were washed with H2O. The aqueous phase was extracted with additional dichloromethane and the combined organic fractions were then washed with brine, dried (Na2SO4) and filtered. The filtrate was concentrated under reduced pressure and the crude product was purified by preparative HPLC. The product was free-based by partitioning between a saturated solution of NaHCO3 and dichloromethane. The organic layer was then separated, dried (Na2SO4), filtered and concentrated under reduced pressure to give 1-[2-(4-biphenyl-2-ylmethyl-piperazin-1-yl)-thiazol-4-ylmethyl]-3-[3-(4-fluoro-phenoxy)-propyl]-1,3-dihydro-benzoimidazol-2-ylideneamine (3.6 mg, 8%). HPLC-MS 633 [M+1]+, 317 (100%).

후처리

  1. temperatureAfter this time, the suspension was cooled to rt
  2. filtrationfiltered through Celite®
  3. washThe collected solids were washed with dichloromethane
  4. washthe combined filtrate and washings were washed with H2O
  5. extractionThe aqueous phase was extracted with additional dichloromethane
  6. washthe combined organic fractions were then washed with brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated under reduced pressure
  10. customthe crude product was purified by preparative HPLC
  11. customby partitioning between a saturated solution of NaHCO3 and dichloromethane
  12. customThe organic layer was then separated
  13. dry with materialdried (Na2SO4)
  14. filtrationfiltered
  15. concentrationconcentrated under reduced pressure

출처 및 근거

ORD 기록
ord-82e2ab4ea8e84eb888013b02f7f65b35
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08759520B2

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