Cesium carbonate → 7-[2-(4-Benzyloxy-6-oxo-6H-pyridazin-1-yl)-ethyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic Acid Tert-Butyl Ester

HRID 564186Notes

Reaction equation

HRID 564186 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[N:13][NH:12][C:11](=[O:15])[CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[C:22]([O:26][C:27]([N:29]1[CH2:38][CH2:37][C:36]2[C:31](=[CH:32][C:33]([CH2:39][CH2:40]I)=[CH:34][CH:35]=2)[CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]>CN(C=O)C>[C:22]([O:26][C:27]([N:29]1[CH2:38][CH2:37][C:36]2[C:31](=[CH:32][C:33]([CH2:39][CH2:40][N:12]3[C:11](=[O:15])[CH:10]=[C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[CH:14]=[N:13]3)=[CH:34][CH:35]=2)[CH2:30]1)=[O:28])([CH3:25])([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 580428517-(2-iodoethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl esterHCID 598221075-(benzyloxy)pyridazin-3(2H)-one

Product 1

HCID 670069227-[2-(4-Benzyloxy-6-oxo-6H-pyridazin-1-yl)-ethyl]-3,4-dihydro-1H-isoquinoline-2-carboxylic Acid Tert-Butyl Ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To 245 mg (1.21 mmol) 5-benzyloxy-2H-pyridazin-3-one (preparation 5c) in 1.2 mL DMF is added 791 mg (2.43 mmol) cesium carbonate and after 15 min 470 mg (1.21 mmol) 7-(2-iodoethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (preparation 8). The reaction mixture is stirred overnight at RT and the precipitate is removed by filtration. The solvent is evaporated, the residue is dissolved in DMF and purified via reverse HPLC chromatography (Waters symmetry, C18; water (0.15% formic acid)/acetonitrile 95:5 to 10:90).

Workup

  1. customthe precipitate is removed by filtration
  2. customThe solvent is evaporated
  3. dissolutionthe residue is dissolved in DMF
  4. custompurified via reverse HPLC chromatography (Waters symmetry, C18; water (0.15% formic acid)/acetonitrile 95:5 to 10:90)

Sources & evidence

ORD record
ord-4658ae456c5c42aba38cfd9a9799c37f
Source dataset
uspto-grants-2011_11
Patent number
US08067590B2

Reaction notes

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