Potassium Carbonate → 6-tert-butyl-2-{3-[5-(1'-ethyl-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-6-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-one

HRID 449625Notes

Reaction equation

HRID 449625 reaction equation
C([O:4][CH2:5][C:6]1[C:11]([C:12]2[CH:17]=[C:16]([NH:18][C:19]3[CH:24]=[CH:23][C:22]([CH:25]4[CH2:30][CH2:29][N:28]([CH2:31][CH3:32])[CH2:27][CH2:26]4)=[CH:21][N:20]=3)[C:15](=[O:33])[N:14]([CH3:34])[N:13]=2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:35]1[N:44]=[CH:43][C:42]2[C:37](=[C:38]([F:49])[CH:39]=[C:40]([C:45]([CH3:48])([CH3:47])[CH3:46])[CH:41]=2)[C:36]1=[O:50])(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO>[C:45]([C:40]1[CH:41]=[C:42]2[C:37](=[C:38]([F:49])[CH:39]=1)[C:36](=[O:50])[N:35]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([C:12]3[CH:17]=[C:16]([NH:18][C:19]4[N:20]=[CH:21][C:22]([CH:25]5[CH2:30][CH2:29][N:28]([CH2:31][CH3:32])[CH2:27][CH2:26]5)=[CH:23][CH:24]=4)[C:15](=[O:33])[N:14]([CH3:34])[N:13]=3)[C:6]=1[CH2:5][OH:4])[N:44]=[CH:43]2)([CH3:46])([CH3:47])[CH3:48]

Participants

4

Reactant 2

HCID 11430Potassium CarbonateHCID 667432512-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(1-ethylpiperidin-4-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate

Product 1

HCID 566558096-tert-butyl-2-{3-[5-(1'-ethyl-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-6-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-oneYield 78.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
40 °C

Procedure

To 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(5-(5-(1-ethylpiperidin-4-yl)pyridin-2-ylamino)-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl)benzyl acetate (147 mg, 216 μmol, Eq: 1.00) in MeOH (15 ml) was added potassium carbonate (59.8 mg, 432 μmol, Eq: 2.0). The reaction mixture stirred at 40° C. for 1 h. The solution was cooled to room temperature. Concentrated in vacuo. The residue was taken up in DCM/water and the layers were separated. The aqueous layer was extracted once with DCM. The organic layers were combined, and then dried over Na2SO4. Concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 12 g, 25% to 75% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient) to give 6-tert-butyl-2-{3-[5-(1′-ethyl-1′,2′,3′,4′,5′,6′-hexahydro-[3,4′]bipyridinyl-6-ylamino)-1-methyl-6-oxo-1,6-dihydro-pyridazin-3-yl]-2-hydroxymethyl-phenyl}-8-fluoro-2H-phthalazin-1-one (108 mg, 78%). LC/MS-ESI observed [M+H]+ 638. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 1.16 (br. s., 2H) 1.43 (s, 9H) 1.84 (br. s., 4H) 2.06 (br. s., 2H) 2.51 (br. s., 3H) 3.11 (br. s., 2H) 3.69-4.09 (m and overlapping singlet, 4H) 4.42 (d, J=6.80 Hz, 2H) 6.91 (d, J=8.69 Hz, 1H) 7.37-7.77 (m, 6H) 8.11-8.36 (m, 3H) 8.60 (s, 1H)

Workup

  1. temperatureThe solution was cooled to room temperature
  2. concentrationConcentrated in vacuo
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted once with DCM
  5. dry with materialdried over Na2SO4
  6. concentrationConcentrated in vacuo
  7. customThe crude material was purified by flash chromatography (silica gel, 12 g, 25% to 75% (60:10:1 DCM:MeOH:NH4OH)/DCM gradient)

Sources & evidence

ORD record
ord-c040560b83ca49bca9f9a8618d705007
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

Loading…