Triethylamine → AZD4694 Precursor

HRID 627316Notes

Reaction equation

HRID 627316 reaction equation
[CH2:1]([O:3][CH2:4][O:5][C:6]1[CH:7]=[CH:8][C:9]2[O:13][C:12](B(O)O)=[CH:11][C:10]=2[CH:17]=1)[CH3:2].[C:18]([O:22][C:23](=[O:36])[N:24]([C:26]1[CH:31]=[CH:30][C:29](Br)=[C:28]([N+:33]([O-:35])=[O:34])[N:27]=1)[CH3:25])([CH3:21])([CH3:20])[CH3:19].CCN(CC)CC>C(O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:18]([O:22][C:23](=[O:36])[N:24]([C:26]1[CH:31]=[CH:30][C:29]([C:12]2[O:13][C:9]3[CH:8]=[CH:7][C:6]([O:5][CH2:4][O:3][CH2:1][CH3:2])=[CH:17][C:10]=3[CH:11]=2)=[C:28]([N+:33]([O-:35])=[O:34])[N:27]=1)[CH3:25])([CH3:21])([CH3:19])[CH3:20]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 461839705-Ethoxymethoxy-benzofuran-2-boronic acidHCID 46183971(5-Bromo-6-nitro-pyridin-2-yl)-methyl-carbamic acid tert-butyl ester

Product 1

HCID 46183972AZD4694 PrecursorYield 58%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To a degassed solution of 5-ethoxymethoxy-benzofuran boronic acid (4) (0.69 g, 2.63 mmol) in ethanol (17.5 mL), (5-bromo-6-nitro-pyridin-2-yl)-methyl-carbamic acid tert-butyl ester 12 (0.50 g, 1.51 mmol), Pd(PPh3)2Cl2 (0.14 g, 0.20 mmol) and Et3N (0.48 mL, 3.46 mmol) were added. The reaction mixture was stirred at 90° C. for 30 minutes. The reaction mixture was cooled to 0° C. and clear filtered. Volatiles were removed under reduced pressure. The residue was diluted with water and the mixture was extracted with ethyl acetate. The organic extract was washed with brine and concentrated under reduced pressure. The crude product was purified by flash column chromatography. Evaporation of solvent gave title compound 13 (58% yield).

Workup

  1. temperatureThe reaction mixture was cooled to 0° C.
  2. customVolatiles were removed under reduced pressure
  3. additionThe residue was diluted with water
  4. extractionthe mixture was extracted with ethyl acetate
  5. extractionThe organic extract
  6. washwas washed with brine
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by flash column chromatography
  9. customEvaporation of solvent

Sources & evidence

ORD record
ord-e5bf0dcf801846ee908d60549354a727
Source dataset
uspto-grants-2016_04
Patent number
US09309267B2

Reaction notes

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