Oxalyl chloride → N-(5-cyano-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide

HRID 1497853

Reaktionsgleichung

Reaktionsgleichung von HRID 1497853
[N:1]1[CH:2]=[C:3]([C:10]([OH:12])=O)[N:4]2[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=12.C(Cl)(=O)C(Cl)=O.[NH2:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][C:27]=1[CH3:28])[C:23]#[N:24]>ClCCl.CN(C=O)C.CO.ClC(Cl)C.N(CC)(CCC)CCC>[C:23]([C:22]1[CH:25]=[CH:26][C:27]([CH3:28])=[C:20]([NH:19][C:10]([C:3]2[N:4]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]3=[N:1][CH:2]=2)=[O:12])[CH:21]=1)#[N:24]

Komponenten

9

Edukt 3

HCID 65578Oxalyl chlorideHCID 73142Imidazo(1,2-a)pyridine-3-carboxylic acidHCID 70164283-Amino-4-methylbenzonitrile

Produkt 1

HCID 71280318N-(5-cyano-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamideAusbeute 35,5 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 63651,1-DichloroethaneLösungsmittel2×HCID 519799N,N-DipropylethylamineLösungsmittel

Versuchsvorschrift

To a suspension of imidazo[1,2-a]pyridine-3-carboxylic acid (1) (16.6 g, 102 mmol) in dichloromethane (300 mL) and DMF (0.5 mL) at 0° C. was added oxalyl chloride (45 mL, 510 mmol) dropwise over 10 minutes. The reaction was slowly warmed to room temperature and stirred until complete conversion was detected by LCMS in MeOH. The reaction was subsequently reduced to dryness and suspended in dichloroethane (100 mL) and was added to a solution of 3-amino-4-methylbenzonitrile (7) (15 g, 113 mmol) in dichloroethane (200 mL) and Pr2NEt (55 mL) at 0° C. After the addition, the cold bath was removed and contents were stirred at room temperature for 1 hour and then heated to 50° C. for another 2 hours. After the completion of the reaction, the mixture was cooled and a white precipitate formed. The mixture was filtered and the solid was washed with cold dichloromethane. About 10 g of the desired N-(5-cyano-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (8) was obtained. The filtrate was washed with saturated NH4Cl, saturated NaHCO3, brine, dried over magnesium sulfate, filtered and reduced to dryness. The crude solid was triturated with diethyl ether to remove excess aniline and filtered to afford another crop of N-(5-cyano-2-methylphenyl)imidazo[1,2-a]pyridine-3-carboxamide (8) as a white solid. MS m/z 277.1 (M+1).

Aufarbeitung

  1. additionAfter the addition
  2. customthe cold bath was removed
  3. stirringcontents were stirred at room temperature for 1 hour
  4. temperatureheated to 50° C. for another 2 hours
  5. customAfter the completion of the reaction
  6. temperaturethe mixture was cooled
  7. customa white precipitate formed
  8. filtrationThe mixture was filtered
  9. washthe solid was washed with cold dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-c01d8ab89604425cbe9b7634c7a2ac74
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09199981B2

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