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]pyridin-6-yl}-benzyl ester

HRID 402947Notes

Reaction equation

HRID 402947 reaction equation
Br[C:2]1[CH:3]=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][C:15]([C:18]([N:20]3[CH2:25][CH2:24][O:23][CH2:22][CH2:21]3)=[O:19])=[CH:14][CH:13]=2)[C:5]2[N:6]([CH:8]=[CH:9][N:10]=2)[CH:7]=1.[C:26]([O:29][CH2:30][C:31]1[C:36](B2OC(C)(C)C(C)(C)O2)=[CH:35][CH:34]=[CH:33][C:32]=1[N:46]1[N:55]=[CH:54][C:53]2[C:48](=[C:49]([F:60])[CH:50]=[C:51]([C:56]([CH3:59])([CH3:58])[CH3:57])[CH:52]=2)[C:47]1=[O:61])(=[O:28])[CH3:27].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:56]([C:51]1[CH:52]=[C:53]2[C:48](=[C:49]([F:60])[CH:50]=1)[C:47](=[O:61])[N:46]([C:32]1[CH:33]=[CH:34][CH:35]=[C:36]([C:2]3[CH:3]=[C:4]([NH:11][C:12]4[CH:17]=[CH:16][C:15]([C:18]([N:20]5[CH2:25][CH2:24][O:23][CH2:22][CH2:21]5)=[O:19])=[CH:14][CH:13]=4)[C:5]4[N:6]([CH:8]=[CH:9][N:10]=4)[CH:7]=3)[C:31]=1[CH2:30][O:29][C:26](=[O:28])[CH3:27])[N:55]=[CH:54]2)([CH3:57])([CH3:58])[CH3:59]

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 86686844[4-(6-Bromo-imidazo[1,2-a]pyridin-8-ylamino)-phenyl]-morpholin-4-yl-methanone

Product 1

HCID 86686845acetic acid 2-(6-tert-butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-{8-[4-(morpholine-4-carbonyl)-phenylamino]-imidazo[1,2-a]pyridin-6-yl}-benzyl esterYield 25%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

[4-(6-Bromo-imidazo[1,2-a]pyridin-8-ylamino)-phenyl]-morpholin-4-yl-methanone (270 mg, 0.68 mmol), 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 (670 mg, 1.35 mmol) and K2CO3 (188 mg, 1.36 mmol) were dissolved in a 10:1 mixture of dioxane in H2O (11 ml). Under N2 atmosphere, Pd2(dba)3 (62 mg, 0.068 mmol) and X-phos (129 mg, 0.27 mmol) were added and the mixture was stirred at reflux temperature overnight. After the completion of the reaction, the mixture was cooled to room temperature, poured into water (100 mL) and extracted by DCM (100 ml). The organic extracts were washed with saturated aqueous solution of sodium chloride (100 ml), dried over sodium sulfate and concentrated. The residue was purified by silica gel column (petroleum ether:ethyl acetate 2:1) to afford the desired product as a yellow solid (60 mg, yield 25%). LC-MS: 689[M+1]+, tR=1.506 min.

Workup

  1. temperatureat reflux temperature overnight
  2. customAfter the completion of the reaction
  3. extractionextracted by DCM (100 ml)
  4. washThe organic extracts were washed with saturated aqueous solution of sodium chloride (100 ml)
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column (petroleum ether:ethyl acetate 2:1)

Sources & evidence

ORD record
ord-69e2e985032242e192e2a9fb05d53df2
Source dataset
uspto-grants-2014_06
Patent number
US08742098B2

Reaction notes

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