Dimethylacetamide → [(4-Cyano-7-hydroxy-2-phenyl-thiazolo[5,4-c]pyridine-6-carbonyl)-amino]-acetic acid

HRID 642374Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 642374
Br[C:2]1[C:7]2[S:8][C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[N:10][C:6]=2[C:5]([OH:17])=[C:4]([C:18]([NH:20][CH2:21][C:22]([OH:24])=[O:23])=[O:19])[N:3]=1.C[C:26]([N:28](C)C)=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].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[C-]#N.[Zn+2].[C-]#N.[Zn]>[C:26]([C:2]1[C:7]2[S:8][C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[N:10][C:6]=2[C:5]([OH:17])=[C:4]([C:18]([NH:20][CH2:21][C:22]([OH:24])=[O:23])=[O:19])[N:3]=1)#[N:28]

Komponenten

7

Edukt 2

HCID 31374DimethylacetamideHCID 86617359[(4-Bromo-7-hydroxy-2-phenyl-thiazolo[5,4-c]pyridine-6-carbonyl)-amino]-acetic acid

Produkt 1

HCID 24757418[(4-Cyano-7-hydroxy-2-phenyl-thiazolo[5,4-c]pyridine-6-carbonyl)-amino]-acetic acid

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 23994ZincKatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of [(4-bromo-7-hydroxy-2-phenyl-thiazolo[5,4-c]pyridine-6-carbonyl)-amino]-acetic acid (130 mg, 0.32 mmole), tris(dibenzylideneacetone)dipalladium(0)(15 mg, 0.02 mmole), 1,1′-bis(diphenylphosphino)ferrocene (18 mg, 0.04 mmole), zinc cyanide (23 mg, 0.19 mmole) and zinc (3 mg, 0.04 mmole) in dimethylacetamide (640 μl) was stirred at 120° C. for 3 h before it was cooled to room temperature, partitioned between ethyl acetate and 1N NaOH (50 ml). The aqueous layer was acidified with 5 N HCl (10 ml) to pH=2, extracted with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified by column chromatography on a C18 column with a gradient of water and acetonitrile in formic acid to give the title compound as a yellow solid (46 mg). MS: (+) m/z 355.22 (M+1), MS: (−) m/z 353.18 (M−1).

Aufarbeitung

  1. temperaturewas cooled to room temperature
  2. custompartitioned between ethyl acetate and 1N NaOH (50 ml)
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chromatography on a C18 column with a gradient of water and acetonitrile in formic acid

Quellen und Nachweise

ORD-Eintrag
ord-824950923d2c4fc8b91b07223e066c6e
Quelldatensatz
uspto-grants-2010_04
Patentnummer
US07696223B2

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