Oxalyl chloride → 10a-(4-methoxyphenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-5-oxo-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazine-8-carbonitrile

HRID 1753165

Reaktionsgleichung

Reaktionsgleichung von HRID 1753165
C(Cl)(=O)C(Cl)=O.[CH3:7][C:8]1[C:12]([C:13]([OH:15])=O)=[CH:11][O:10][N:9]=1.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]23[NH:38][CH2:37][CH2:36][N:25]2[C:26](=[O:35])[C:27]2[N:28]([C:30]([C:33]#[N:34])=[CH:31][CH:32]=2)[CH2:29]3)=[CH:20][CH:19]=1>CN(C=O)C.C(Cl)Cl.N1C=CC=CC=1.O>[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]23[N:38]([C:13]([C:12]4[C:8]([CH3:7])=[N:9][O:10][CH:11]=4)=[O:15])[CH2:37][CH2:36][N:25]2[C:26](=[O:35])[C:27]2[N:28]([C:30]([C:33]#[N:34])=[CH:31][CH:32]=2)[CH2:29]3)=[CH:20][CH:19]=1

Komponenten

8

Edukt 3

HCID 65578Oxalyl chlorideHCID 45896923-Methyl-1,2-oxazole-4-carboxylic acidHCID 6736752410a-(4-methoxyphenyl)-5-oxo-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]-pyrazine-8-carbonitrile

Produkt 1

HCID 5337330010a-(4-methoxyphenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-5-oxo-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazine-8-carbonitrileAusbeute 40,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 6228DimethylformamideKatalysatorHCID 962WaterLösungsmittelHCID 1049PyridineLösungsmittel2×HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To generate the acid chloride, oxalyl chloride (150 μL, 1.61 mmol) and DMF (1 drop) were added to a suspension of 3-methyl-1,2-oxazole-4-carboxylic acid (65 mg, 0.51 mmol) in CH2Cl2 (1 mL) at 0° C. The suspension was allowed to stir for a further 15 minutes at 0° C. followed by 1 hour at room temperature. The resulting solution was concentrated in vacuo (without heating) to give an oil that was dissolved in CH2Cl2 and concentrated in vacuo. To a chilled (ice bath) suspension of the acid chloride (generated as above, 0.51 mmol) in pyridine (1 mL) was added a cloudy mixture of 10a-(4-methoxyphenyl)-5-oxo-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]-pyrazine-8-carbonitrile (45 mg, 0.1 mmol) in pyridine (1 mL). The reaction mixture was warmed to room temperature and stirred for 1.5 hour. The reaction mixture was then diluted with water (5 mL) and extracted with CH2Cl2 (3×2 mL). The organic fractions were combined, dried (MgSO4) and concentrated in vacuo to yield a crude residue that was purified by flash chromatography (Biotage SP4, 4 g cartridge, gradient 0-100% EtOAc in hexanes) and reverse phase chromatography (Biotage SP4.12 g cartridge, C18, 5-50s-55-100% acetonitrile in water; water contained 0.1% formic acid) to give 10a-(4-methoxyphenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-5-oxo-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazine-8-carbonitrile (106) as a white solid (17 mg, yield 40%).

Aufarbeitung

  1. waitfollowed by 1 hour at room temperature
  2. concentrationThe resulting solution was concentrated in vacuo (without heating)
  3. customto give an oil that
  4. concentrationconcentrated in vacuo
  5. temperatureTo a chilled
  6. additionwas added
  7. temperatureThe reaction mixture was warmed to room temperature
  8. stirringstirred for 1.5 hour
  9. extractionextracted with CH2Cl2 (3×2 mL)
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated in vacuo
  12. customto yield a crude residue that
  13. customwas purified by flash chromatography (Biotage SP4, 4 g cartridge, gradient 0-100% EtOAc in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-1053018bdc16487ab8c0239431a8ecfa
Quelldatensatz
uspto-grants-2015_10
Patentnummer
US09163029B2

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