Acetonitrile → 4-(3-((7-Methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-2-methylbut-3-yn-2-ol

HRID 40217

반응식

HRID 40217 반응식
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH2:11][O:12][C:13]3[C:22]4[C:17](=[CH:18][C:19]([O:23][CH3:24])=[CH:20][CH:21]=4)[N:16]=[CH:15][CH:14]=3)=[N:9][N:10]=2)[N:7]=1.[CH3:25][C:26]([OH:30])([C:28]#[CH:29])[CH3:27].C(N(CC)CC)C.C(#N)C>[Cu]I>[CH3:24][O:23][C:19]1[CH:18]=[C:17]2[C:22]([C:13]([O:12][CH2:11][C:8]3[N:6]4[N:7]=[C:2]([C:29]#[C:28][C:26]([CH3:27])([OH:30])[CH3:25])[CH:3]=[CH:4][C:5]4=[N:10][N:9]=3)=[CH:14][CH:15]=[N:16]2)=[CH:21][CH:20]=1

참가 물질

6

반응물 4

HCID 6342AcetonitrileHCID 82582-Methyl-3-butyn-2-olHCID 8471TriethylamineHCID 250669924-((6-Chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline

생성물 1

HCID 576912104-(3-((7-Methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-2-methylbut-3-yn-2-ol수율 51.3%

시약·촉매·용매 1

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매

반응 조건

온도
90 °C

실험 절차

A 25×200 mm test tube was charged with 4-((6-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3-yl)methoxy)-7-methoxyquinoline (0.150 g, 0.439 mmol), 2-methylbut-3-yn-2-ol (0.213 ml, 2.19 mmol), copper (I) iodide (0.0209 g, 0.110 mmol), triethylamine (1.83 ml, 13.2 mmol), and acetonitrile (5.00 ml, 96.2 mmol), flushed with argon, sealed, and placed in a 90° C. oil bath for 30 minutes. PdCl2(dppf)-CH2Cl2Adduct (0.0358 g, 0.0439 mmol) was added in one portion, the tube flushed with argon, sealed, then heated in a 90° C. oil bath for 4 hours. The reaction mixture was filtered thru a pad of silica gel (eluting with EtOAc/DCM/MeOH), then concentrated to yield a dark brown oil. This was purified by MPLC, using a 40 g RediSep column, eluting with 1-7% MeOH/DCM over 40 minutes. The appropriate fractions were collected to give 4-(3-((7-methoxyquinolin-4-yloxy)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-2-methylbut-3-yn-2-ol (0.0877 g, 51.3% yield).

후처리

  1. customflushed with argon
  2. customsealed
  3. customplaced in a 90° C.
  4. customfor 30 minutes
  5. customthe tube flushed with argon
  6. customsealed
  7. filtrationThe reaction mixture was filtered
  8. concentrationconcentrated
  9. customto yield a dark brown oil
  10. customThis was purified by MPLC
  11. washeluting with 1-7% MeOH/DCM over 40 minutes
  12. customThe appropriate fractions were collected

출처 및 근거

ORD 기록
ord-adbe44e359d74261bb97ca1e845bb0d2
출처 데이터셋
uspto-grants-2013_09
특허 번호
US08524900B2

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