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

HRID 642374Notes

Reaction equation

HRID 642374 reaction equation
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]

Participants

7

Reactant 2

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-824950923d2c4fc8b91b07223e066c6e
Source dataset
uspto-grants-2010_04
Patent number
US07696223B2

Reaction notes

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