Potassium Carbonate → acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{8-[4-(1-methyl-piperidin-4-yl)-phenylamino]-imidazo[1,2-a]pyrazin-6-yl}-benzyl ester

HRID 402943Notes

Reaction equation

HRID 402943 reaction equation
[C:1]([O:4][CH2:5][C:6]1[C:11](B2OC(C)(C)C(C)(C)O2)=[CH:10][CH:9]=[CH:8][C:7]=1[N:21]1[N:30]=[CH:29][C:28]2[C:23](=[C:24]([F:35])[CH:25]=[C:26]([C:31]([CH3:34])([CH3:33])[CH3:32])[CH:27]=2)[C:22]1=[O:36])(=[O:3])[CH3:2].Br[C:38]1[N:39]=[C:40]([NH:47][C:48]2[CH:53]=[CH:52][C:51]([CH:54]3[CH2:59][CH2:58][N:57]([CH3:60])[CH2:56][CH2:55]3)=[CH:50][CH:49]=2)[C:41]2[N:42]([CH:44]=[CH:45][N:46]=2)[CH:43]=1.C([O-])([O-])=O.[K+].[K+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:31]([C:26]1[CH:27]=[C:28]2[C:23](=[C:24]([F:35])[CH:25]=1)[C:22](=[O:36])[N:21]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]([C:38]3[N:39]=[C:40]([NH:47][C:48]4[CH:49]=[CH:50][C:51]([CH:54]5[CH2:59][CH2:58][N:57]([CH3:60])[CH2:56][CH2:55]5)=[CH:52][CH:53]=4)[C:41]4[N:42]([CH:44]=[CH:45][N:46]=4)[CH:43]=3)[C:6]=1[CH2:5][O:4][C:1](=[O:3])[CH3:2])[N:30]=[CH:29]2)([CH3:33])([CH3:32])[CH3:34]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 594737692-(6-(tert-Butyl)-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetateHCID 86686841(6-Bromo-imidazo[1,2-a]pyrazin-8-yl)-[4-(1-methyl-piperidin-4-yl)-phenyl]-amine

Product 1

HCID 86686842acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{8-[4-(1-methyl-piperidin-4-yl)-phenylamino]-imidazo[1,2-a]pyrazin-6-yl}-benzyl esterYield 92%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of 2-(6-tert-butyl-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate (491.3 mg, 1 mmol), (6-bromo-imidazo[1,2-a]pyrazin-8-yl)-[4-(1-methyl-piperidin-4-yl)-phenyl]-amine (200 mg, 0.52 mmol), K2CO3 (137 mg, 1 mmol), Pd2(dba)3 (45.4 mg, 0.05 mmol), X-phos (94.5 mg, 0.2 mmol) in 30 mL dioxane and 10 mL water was stirred at 90° C. overnight. The reaction mixture was filtered. The filtrate was evaporated and the residue was purified through a silica-gel column (ethyl acetate:petroleum ether=1:2) to give the desired product as a yellow oil (320 mg, 92% yield).

Workup

  1. filtrationThe reaction mixture was filtered
  2. customThe filtrate was evaporated
  3. customthe residue was purified through a silica-gel column (ethyl acetate:petroleum ether=1:2)

Sources & evidence

ORD record
ord-b689948e984344619e7e72c0b056d3f9
Source dataset
uspto-grants-2014_06
Patent number
US08742098B2

Reaction notes

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