Sodium Iodide → 6-(3-Chloro-4-(4,5-dihydro-1H-imidazol-2-yl)phenyl)-2-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridazin-3(2H)-one

HRID 1878783노트

반응식

HRID 1878783 반응식
[NH2:1][CH2:2][CH2:3][NH:4][C:5](=O)[C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15](=[O:18])[N:14]([CH2:19][CH2:20][O:21][C:22]3[C:31]4[C:26](=[CH:27][C:28]([O:32][CH3:33])=[CH:29][CH:30]=4)[N:25]=[CH:24][CH:23]=3)[N:13]=2)=[CH:8][C:7]=1[Cl:34].Cl[Si](C)(C)C.[I-].[Na+]>C(Cl)Cl>[Cl:34][C:7]1[CH:8]=[C:9]([C:12]2[CH:17]=[CH:16][C:15](=[O:18])[N:14]([CH2:19][CH2:20][O:21][C:22]3[C:31]4[C:26](=[CH:27][C:28]([O:32][CH3:33])=[CH:29][CH:30]=4)[N:25]=[CH:24][CH:23]=3)[N:13]=2)[CH:10]=[CH:11][C:6]=1[C:5]1[NH:4][CH2:3][CH2:2][N:1]=1

참가 물질

5

반응물 3

HCID 5238Sodium IodideHCID 6397ChlorotrimethylsilaneHCID 59843092N-(2-aminoethyl)-2-chloro-4-(1-(2-(7-methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzamide

생성물 1

HCID 598430226-(3-Chloro-4-(4,5-dihydro-1H-imidazol-2-yl)phenyl)-2-(2-(7-methoxyquinolin-4-yloxy)ethyl)pyridazin-3(2H)-one

시약·촉매·용매 1

HCID 6344Dichloromethane용매

반응 조건

온도
40 °C

실험 절차

A suspension of N-(2-aminoethyl)-2-chloro-4-(1-(2-(7-methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzamide (50 mg, 101 μmol), chlorotrimethylsilane (39 μl, 304 μmol), sodium iodide (46 mg, 304 μmol), and TEA (42 μL, 304 μmol) in DCM (2 mL) was stirred for 3 hours at 40° C. in an appropriately sealed vial. The reaction was then partitioned between DCM (5 mL) and 1 M NaOH (2 mL). The organic layer was then separated and dried over MgSO4, concentrated onto dry silica (2 g) then purified on silica (4 g) by washing with 5% MeOH, then eluting product with 4->10% NH3 in MeOH (2M)/DCM. The product was isolated as a white solid. (ESI pos. ion) m/z: 476 (MH+); calc'd for C25H22ClN5O3: 475. 1H NMR (400 MHz, DMSO-d6) □ ppm 3.65 (s, 4 H) 3.87 (s, 3 H) 4.69 (dd, J=7.34, 3.42 Hz, 4 H) 6.95 (d, J=5.28 Hz, 1 H) 7.03 (dd, J=9.10, 2.45 Hz, 1 H) 7.12 (d, J=9.78 Hz, 1 H) 7.28 (d, J=2.35 Hz, 1 H) 7.67 (d, J=8.22 Hz, 1 H) 7.83-7.92 (m, 2 H) 7.97 (d, J=1.56 Hz, 1 H) 8.13 (d, J=9.78 Hz, 1H) 8.62 (d, J=5.28 Hz, 1 H).

후처리

  1. customThe reaction was then partitioned between DCM (5 mL) and 1 M NaOH (2 mL)
  2. customThe organic layer was then separated
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated onto dry silica (2 g)
  5. customthen purified on silica (4 g)
  6. washby washing with 5% MeOH
  7. customThe product was isolated as a white solid

출처 및 근거

ORD 기록
ord-450a51b4aa0944ab928353a9b3f646d8
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08314087B2

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