Ammonium Chloride → Methyl 4-[(6-morpholin-4-yl-pyridazin-3-ylamino)-methyl]-benzoate

HRID 852919Notes

Reaction equation

HRID 852919 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.Cl.[NH2:15][CH2:16][C:17]1[CH:26]=[CH:25][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:19][CH:18]=1.[NH4+].[Cl-]>CC(O)C>[N:8]1([C:5]2[N:6]=[N:7][C:2]([NH:15][CH2:16][C:17]3[CH:18]=[CH:19][C:20]([C:21]([O:23][CH3:24])=[O:22])=[CH:25][CH:26]=3)=[CH:3][CH:4]=2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 3210794-(6-Chloropyridazin-3-yl)morpholineHCID 2729253Methyl 4-(aminomethyl)benzoate hydrochloride

Product 1

HCID 58930537Methyl 4-[(6-morpholin-4-yl-pyridazin-3-ylamino)-methyl]-benzoateYield 8.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 64 (2.0 g, 10.0 mmol) and methyl 4-(aminomethyl)benzoate hydrochloride (2.2 g, 11.0 mmol) in i-PrOH (200 mL) was added NH4Cl (2.14 g, 40.0 mmol). The reaction mixture was heated at 150° C. for 72 h and concentrated. The residue was dissolved in water and the aqueous phase was extracted with. \the aqueous phase was separated, treated with 1N NaOH (pH 8) and extracted with EtOAc. The extract was dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by flash chromatography on silica gel (MeOH/CH2Cl2: 2/98 to 5/95) to afford the title compound 65 (270 mg, 0.82 mmol, 8% yield). 1H NMR: (400 MHz, CDCl3) δ (ppm): 7.97 (d, J=8.0 Hz, 2H), 7.42 (d, J=8.0 Hz, 2H), 6.90 (d, J=9.2 Hz, 1H), 6.69 (d, J=9.2 Hz, 1H), 5.16-5.06 (bs, 1H), 4.67 (s, 2H), 3.90 (s, 3H), 3.82 (t, J=4.8 Hz, 4H), 3.41 (t, J=4.8 Hz, 4H).

Workup

  1. concentrationconcentrated
  2. dissolutionThe residue was dissolved in water
  3. extractionthe aqueous phase was extracted with
  4. custom\the aqueous phase was separated
  5. additiontreated with 1N NaOH (pH 8)
  6. extractionextracted with EtOAc
  7. dry with materialThe extract was dried over anhydrous Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography on silica gel (MeOH/CH2Cl2: 2/98 to 5/95)

Sources & evidence

ORD record
ord-89f41a02d34945428ae3af8a28b1dab5
Source dataset
uspto-grants-2007_08
Patent number
US07253204B2

Reaction notes

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