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

HRID 402940Notes

Reaction equation

HRID 402940 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:27]=[CH:26][CH:25]=[C:24](B3OC(C)(C)C(C)(C)O3)[C:18]=1[CH2:19][O:20][C:21](=[O:23])[CH3:22])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].Br[C:38]1[N:39]=[C:40]([NH:47][C:48]2[CH:53]=[CH:52][C:51]([C:54]([N:56]3[CH2:61][CH2:60][O:59][CH2:58][CH2:57]3)=[O:55])=[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: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:27]=[CH:26][CH:25]=[C:24]([C:38]3[N:39]=[C:40]([NH:47][C:48]4[CH:49]=[CH:50][C:51]([C:54]([N:56]5[CH2:61][CH2:60][O:59][CH2:58][CH2:57]5)=[O:55])=[CH:52][CH:53]=4)[C:41]4[N:42]([CH:44]=[CH:45][N:46]=4)[CH:43]=3)[C:18]=1[CH2:19][O:20][C:21](=[O:23])[CH3:22])[N:9]=[CH:8]2)([CH3:2])([CH3:3])[CH3:4]

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 59754722[4-(6-Bromo-imidazo[1,2-a]pyrazin-8-ylamino)-phenyl]-morpholin-4-yl-methanone

Product 1

HCID 86686839acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{8-[4-(morpholine-4-carbonyl)-phenylamino]-imidazo[1,2-a]pyrazin-6-yl}-benzyl esterYield 93%

Reagents, catalysts & solvents 3

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

Procedure

A solution of acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-benzyl ester (491.3 mg, 1 mmol), [4-(6-bromo-imidazo[1,2-a]pyrazin-8-ylamino)-phenyl]-morpholin-4-yl-methanone (200 mg, 0.5 mmol), K2CO3 (137 mg, 1 mmol), Pd2(dba)3 (45.4 mg, 0.05 mmol) and X-Phos (94.5 mg, 0.2 mmol) in 30 mL dioxane and 10 mL water was stirred at 90° C. overnight. The crude reaction mixture was filtered. The filtrate was evaporated and the resulting residue was purified through a silica-gel column (ethyl acetate:petroleum ether=1:2) to give compound the desired product as a yellow oil (320 mg, 93% yield).

Workup

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

Sources & evidence

ORD record
ord-6acd33f12d614667807455d24b9f8623
Source dataset
uspto-grants-2014_06
Patent number
US08742098B2

Reaction notes

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