Potassium Carbonate → 4-[2-acetoxymethyl-3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-phenyl]-pyrrole-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

HRID 1025567Notes

Reaction equation

HRID 1025567 reaction equation
Br[C:2]1[CH:12]=[CH:11][CH:10]=[C:9]([N:13]2[N:22]=[CH:21][C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:23]([CH3:26])([CH3:25])[CH3:24])[CH:19]=3)[C:14]2=[O:27])[C:3]=1[CH2:4][O:5][C:6](=[O:8])[CH3:7].[CH3:28][O:29][C:30]([C:32]1[N:33]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH:34]=[C:35](B2OC(C)(C)C(C)(C)O2)[CH:36]=1)=[O:31].C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:28][O:29][C:30]([C:32]1[N:33]([C:46]([O:48][C:49]([CH3:52])([CH3:51])[CH3:50])=[O:47])[CH:34]=[C:35]([C:2]2[CH:12]=[CH:11][CH:10]=[C:9]([N:13]3[N:22]=[CH:21][C:20]4[C:15](=[CH:16][CH:17]=[C:18]([C:23]([CH3:26])([CH3:24])[CH3:25])[CH:19]=4)[C:14]3=[O:27])[C:3]=2[CH2:4][O:5][C:6](=[O:8])[CH3:7])[CH:36]=1)=[O:31]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 445577501-tert-butyl 2-methyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole-1,2-dicarboxylateHCID 58016210acetic acid 2-bromo-6-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-benzyl ester

Product 1

HCID 710081234-[2-acetoxymethyl-3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-phenyl]-pyrrole-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl esterYield 40%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Under N2, a mixture of acetic acid 2-bromo-6-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-benzyl ester (preparation described in intermediate-4, 300 mg, 0.699 mmol), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyrrole-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (270 mg, 0.769 mmol), Pd(dppf)Cl2 (171 mg, 0.21 mmol) and K2CO3 (289 mg, 2.19 mmol) in dioxane (15 mL) and water (3 mL) was heated at 100° C. for 4 h. The mixture was concentrated to dryness. The residue was purified by silica gel column chromatography (eluted with petroleum ether/ethyl acetate with a ratio of 2/1) to give 4-[2-acetoxymethyl-3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-phenyl]-pyrrole-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (160 mg, yield 40%). LC-MS calcd for C32H35N3O7 (m/e) 573.25, obsd 473 [M-Boc+1]+.

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. customThe residue was purified by silica gel column chromatography (
  3. washeluted with petroleum ether/ethyl acetate with a ratio of 2/1)

Sources & evidence

ORD record
ord-b6589b0fab3a46ab88ecb071de888960
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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