P-Toluenesulfonylhydrazide → tert-Butyl 4-(8-morpholino-2-(2-(5,6,7,8-tetrahydroquinolin-2-yl)ethyl)imidazo[1,2-b]pyridazin-3-yl)benzoate

HRID 718674Notes

Reaction equation

HRID 718674 reaction equation
[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[N:9]([C:13]([C:28]4[CH:40]=[CH:39][C:31]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])=[CH:30][CH:29]=4)=[C:14](/[CH:16]=[CH:17]/[C:18]4[CH:27]=[CH:26][C:25]5[CH2:24][CH2:23][CH2:22][CH2:21][C:20]=5[N:19]=4)[N:15]=3)[N:10]=[CH:11][CH:12]=2)[CH2:3][CH2:2]1.CC1C=CC(S(NN)(=O)=O)=CC=1.C([O-])(=O)C.[Na+]>COCCOC.O>[O:1]1[CH2:6][CH2:5][N:4]([C:7]2[C:8]3[N:9]([C:13]([C:28]4[CH:29]=[CH:30][C:31]([C:32]([O:34][C:35]([CH3:36])([CH3:37])[CH3:38])=[O:33])=[CH:39][CH:40]=4)=[C:14]([CH2:16][CH2:17][C:18]4[CH:27]=[CH:26][C:25]5[CH2:24][CH2:23][CH2:22][CH2:21][C:20]=5[N:19]=4)[N:15]=3)[N:10]=[CH:11][CH:12]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 15303P-ToluenesulfonylhydrazideHCID 517045Sodium AcetateHCID 117732516(E)-tert-Butyl 4-(8-morpholino-2-(2-(5,6,7,8-tetrahydroquinolin-2-yl)vinyl)imidazo[1,2-b]pyridazin-3-yl)benzoate

Product 1

HCID 117732518tert-Butyl 4-(8-morpholino-2-(2-(5,6,7,8-tetrahydroquinolin-2-yl)ethyl)imidazo[1,2-b]pyridazin-3-yl)benzoate

Reagents, catalysts & solvents 1

HCID 18180031Water 1,2-dimethoxyethaneSolvent

Procedure

A mixture of compound 60a (60.0 mg, 0.112 mmol), 4-methylbenzenesulfonohydrazide (104 mg, 0.558 mmol) and sodium acetate (46.2 mg, 0.558 mmol) in 3.3 mL of 10:1 DME/water was refluxed for 4 h. After cooling to rt, the mixture was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (0:1-3:2 EtOAc/DCM) to afford compound 60b as a colorless oil. 1H-NMR (CDCl3; 400 MHz) δ 8.05 (d, J=8.6 Hz, 2H), 7.96 (d, J=5.6 Hz, 1H), 7.57 (d, J=8.6 Hz, 2H), 7.15 (d, J=7.6 Hz, 1H), 6.76 (d, J=7.6 Hz, 1H), 6.07 (d, J=5.6 Hz, 1H), 3.96-4.03 (m, 4H), 3.89-3.96 (m, 4H), 3.15-3.30 (m, 4H), 2.83 (t, J=6.3 Hz, 2H), 2.69 (t, J=6.3 Hz, 2H), 1.82-1.91 (m, 2H), 1.73-1.82 (m, 2H), 1.61 (s, 9H). Mass spectrum (ESI, m/z): Calcd. for C32H37N5O3, 540.3 (M+H). found 540.5.

Workup

  1. temperaturewas refluxed for 4 h
  2. concentrationthe mixture was concentrated in vacuo
  3. customthe residue was purified by flash column chromatography on silica gel (0:1-3:2 EtOAc/DCM)

Sources & evidence

ORD record
ord-3a5d630a1f97477da99dcaa8b72e9540
Source dataset
uspto-grants-2015_11
Patent number
US09193736B2

Reaction notes

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