Potassium Carbonate → 5-[2-acetoxymethyl-3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-phenyl]-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester

HRID 1025570Notes

Reaction equation

HRID 1025570 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[N:10]([C:16]1[CH:26]=[CH:25][CH:24]=[C:23](B3OC(C)(C)C(C)(C)O3)[C:17]=1[CH2:18][O:19][C:20](=[O:22])[CH3:21])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[CH3:36][O:37][C:38]([C:40]1[N:41]([CH3:46])[C:42](Br)=[CH:43][CH:44]=1)=[O:39].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]>[CH3:36][O:37][C:38]([C:40]1[N:41]([CH3:46])[C:42]([C:23]2[CH:24]=[CH:25][CH:26]=[C:16]([N:10]3[N:9]=[CH:8][C:7]4[C:12](=[CH:13][CH:14]=[C:5]([C:1]([CH3:3])([CH3:4])[CH3:2])[CH:6]=4)[C:11]3=[O:15])[C:17]=2[CH2:18][O:19][C:20](=[O:22])[CH3:21])=[CH:43][CH:44]=1)=[O:39]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 22350505Methyl 5-bromo-1-methyl-1H-pyrrole-2-carboxylateHCID 580162042-(6-tert-butyl-1-oxophthalazin-2(1H)-yl)-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl acetate2×

Product 1

HCID 710081245-[2-acetoxymethyl-3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-phenyl]-1-methyl-1H-pyrrole-2-carboxylic acid methyl esterYield 77%

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-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-6-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzyl ester (described in the preparation of intermediate 4, 300 mg, 0.63 mmol), 5-bromo-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester (150 mg, 0.69 mmol), Pd(dppf)Cl2 (150 mg, 0.19 mmol) and K2CO3 (261 mg, 1.9 mmol) in dioxane (15 mL) and water (3 mL) were heated at 100° C. for 3 h. The mixture was concentrated to dryness. The residue was purified by silica gel column chromatography (eluted with petroleum ether/ethyl acetate from the ratio of 8:1 to 5:1) to give 5-[2-acetoxymethyl-3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-phenyl]-1-methyl-1H-pyrrole-2-carboxylic acid methyl ester (237 mg, yield 77%) as a yellow liquid. LC-MS calcd for C28H29N3O5 (m/e) 487.21, obsd 997 [2M+Na]+.

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 from the ratio of 8:1 to 5:1)

Sources & evidence

ORD record
ord-25d3592834484df2ae16c32ee9f01188
Source dataset
uspto-grants-2014_05
Patent number
US08729078B2

Reaction notes

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