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 1878783Notes

Reaction equation

HRID 1878783 reaction equation
[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

Participants

5

Reactant 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

Product 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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
40 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-450a51b4aa0944ab928353a9b3f646d8
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

Loading…