Ethylenediamine → N-(2-aminoethyl)-2-chloro-4-(1-(2-(7-methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzamide

HRID 1878782Notes

Reaction equation

HRID 1878782 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14](=[O:17])[N:13]([CH2:18][CH2:19][O:20][C:21]3[C:30]4[C:25](=[CH:26][C:27]([O:31][CH3:32])=[CH:28][CH:29]=4)[N:24]=[CH:23][CH:22]=3)[N:12]=2)[CH:8]=[CH:7][C:3]=1[C:4](O)=[O:5].CCN(C(C)C)C(C)C.CN(C(O[N:50]1N=[N:57][C:52]2C=CC=N[C:51]1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N)CN>CN(C=O)C>[NH2:50][CH2:51][CH2:52][NH:57][C:4](=[O:5])[C:3]1[CH:7]=[CH:8][C:9]([C:11]2[CH:16]=[CH:15][C:14](=[O:17])[N:13]([CH2:18][CH2:19][O:20][C:21]3[C:30]4[C:25](=[CH:26][C:27]([O:31][CH3:32])=[CH:28][CH:29]=4)[N:24]=[CH:23][CH:22]=3)[N:12]=2)=[CH:10][C:2]=1[Cl:1]

Participants

6

Reactant 4

HCID 3301EthylenediamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 598430422-Chloro-4-(1-(2-(7-methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzoic acid

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
23 °C

Procedure

A solution of 2-chloro-4-(1-(2-(7-methoxyquinolin-4-yloxy)ethyl)-6-oxo-1,6-dihydropyridazin-3-yl)benzoic acid (494 mg, 1093 μmol), DIEA (191 μL, 1093 μmol), and HATU (416 mg, 1093 μmol) in DMF (5 mL) was stirred at 23° C. for 15 minutes. This dark solution was then added to a second solution of ethylenediamine (730 μL, 10933 μmol) in DMF (2 mL). The reaction was then stirred overnight at 23° C. followed by a partition between 9:1 CHCl3/IPA (75 mL) and NaOH (1 M, 25 mL). The organic was separated, dried over MgSO4, then concentrated onto dry silica (15 g). The product was purified on silica (40 g) eluting with 10% 2 M NH3 in MeOH/DCM, and isolated as a fluffy lyophilized solid from 1:1 ACN/water. MS (ESI pos. ion) m/z: 494 (MH+); calc'd for C25H24ClN5O4: 493. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.71 (t, J=6.27 Hz, 2H) 3.26 (q, J=6.02 Hz, 2 H) 3.87 (s, 3 H) 4.68 (d, J=4.52 Hz, 4 H) 6.95 (d, J=5.52 Hz, 1 H) 7.05 (dd, J=9.29, 2.26 Hz, 1 H) 7.13 (d, J=10.04 Hz, 1 H) 7.28 (d, J=2.01 Hz, 1 H) 7.51-7.58 (m, 1 H) 7.82-7.97 (m, 3 H) 8.13 (d, J=10.04 Hz, 1 H) 8.50 (t, J=5.27 Hz, 1 H) 8.62 (d, J=5.52 Hz, 1 H).

Workup

  1. customa partition between 9:1 CHCl3/IPA (75 mL) and NaOH (1 M, 25 mL)
  2. customThe organic was separated
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated onto dry silica (15 g)
  5. customThe product was purified on silica (40 g)
  6. washeluting with 10% 2 M NH3 in MeOH/DCM
  7. customisolated as a fluffy lyophilized solid from 1:1 ACN/water

Sources & evidence

ORD record
ord-1d6fe375146c48879b917c0d6192489f
Source dataset
uspto-grants-2012_11
Patent number
US08314087B2

Reaction notes

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