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

HRID 449727Notes

Reaction equation

HRID 449727 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]3[CH:28]=[C:27]([NH:29][C:30]4[CH:35]=[CH:34][C:33]([CH:36]5[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]5)=[CH:32][N:31]=4)[C:26](=[O:42])[N:25]([CH3:43])[N:24]=3)[C:18]=1[CH2:44][OH:45])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[K+].[K+].FC(F)(F)S(O[CH2:58][C:59]([F:62])([F:61])[F:60])(=O)=O.CCOC(C)=O>CN(C=O)C.O>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([C:23]3[CH:28]=[C:27]([NH:29][C:30]4[N:31]=[CH:32][C:33]([CH:36]5[CH2:41][CH2:40][N:39]([CH2:58][C:59]([F:62])([F:61])[F:60])[CH2:38][CH2:37]5)=[CH:34][CH:35]=4)[C:26](=[O:42])[N:25]([CH3:43])[N:24]=3)[C:18]=1[CH2:44][OH:45])[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 803662,2,2-Trifluoroethyl trifluoromethanesulfonateHCID 566563386-tert-butyl-8-fluoro-2-(2-(hydroxymethyl)-3-(1-methyl-6-oxo-5-(5-(piperidin-4-yl)pyridin-2-ylamino)-1,6-dihydropyridazin-3-yl)phenyl)phthalazin-1(2H)-one

Product 1

HCID 566558126-tert-butyl-8-fluoro-2-(2-hydroxymethyl-3-{1-methyl-6-oxo-5-[1'-(2,2,2-trifluoro-ethyl)-1',2',3',4',5',6'-hexahydro-[3,4']bipyridinyl-6-ylamino]-1,6-dihydro-pyridazin-3-yl}-phenyl)-2H-phthalazin-1-oneYield 70.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-tert-butyl-8-fluoro-2-(2-(hydroxymethyl)-3-(1-methyl-6-oxo-5-(5-(piperidin-4-yl)pyridin-2-ylamino)-1,6-dihydropyridazin-3-yl)phenyl)phthalazin-1(2H)-one (10 mg, 16.4 μmol) in DMF (1 ml) was added potassium carbonate (6.8 mg, 49.2 μmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (3.81 mg, 2.36 μl, 16.4 μmol) at room temperature. The mixture was stirred for 8 h. at the same temperature. EtOAc was added into the reaction mixture (10 mL) and the mixture was poured into water (10 mL). Organic layer was separated, washed with water (4×5 mL), dried (Na2SO4), and evaporated under vacuum. Crude product was purified by preparative tlc (CH2Cl2:MeOH:NH4OH, 90:9.5:0.5) to give 8 mg of pure product (70% yield): m/z 692[M+H]+.

Workup

  1. customOrganic layer was separated
  2. washwashed with water (4×5 mL)
  3. dry with materialdried (Na2SO4)
  4. customevaporated under vacuum
  5. customCrude product was purified by preparative tlc (CH2Cl2:MeOH:NH4OH, 90:9.5:0.5)

Sources & evidence

ORD record
ord-58c6079cbd2347df87a2eebb56254ada
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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