Oxalyl chloride → HCID 67369245, compound

HRID 1753150Notes

Reaction equation

HRID 1753150 reaction equation
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.[O:16]=[C:17]1[N:22]2[CH2:23][CH2:24][NH:25][C:21]2([C:26]2[CH:33]=[CH:32][C:29]([C:30]#[N:31])=[CH:28][CH:27]=2)[CH2:20][N:19]2[CH:34]=[CH:35][CH:36]=[C:18]12.C([O-])(O)=O.[Na+]>CN(C=O)C.C(Cl)Cl.N1C=CC=CC=1>[CH3:7][C:8]1[C:12]([C:13]([N:25]2[C:21]3([C:26]4[CH:33]=[CH:32][C:29]([C:30]#[N:31])=[CH:28][CH:27]=4)[CH2:20][N:19]4[CH:34]=[CH:35][CH:36]=[C:18]4[C:17](=[O:16])[N:22]3[CH2:23][CH2:24]2)=[O:15])=[CH:11][O:10][N:9]=1

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 45896923-Methyl-1,2-oxazole-4-carboxylic acidHCID 67367771HCID 67367771, compound

Product 1

HCID 67369245HCID 67369245, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 1049PyridineSolvent2×HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To generate the acid chloride, oxalyl chloride (70 μL, 0.83 mmol) and DMF (1 drop) were added to a suspension of 3-methyl-1,2-oxazole-4-carboxylic acid (50 mg, 0.40 mmol) in CH2Cl2 (0.5 mL) at 0° C. The suspension was allowed to stir for 15 min at 0° C., followed by 2 h at room temperature. The resulting solution was concentrated in vacuo to give a brown oil that was suspended in n-hexanes (2×1 mL) and concentrated in vacuo. To a chilled (ice bath) suspension of the acid chloride (generated as above; 0.40 mmol) in pyridine (0.5 mL) and CH2Cl2 (0.5 mL) was added 4-(5-oxo-2,3-dihydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-10a(10H)-yl)benzonitrile (22 mg, <79 μmol) in pyridine (0.5 mL). The brown reaction mixture was warmed to room temperature and stirred for a further 64 h. Saturated aqueous NaHCO3 (25 mL) was then added and the mixture extracted with CH2Cl2 (3×25 mL). The organic fractions were combined, dried (MgSO4) and concentrated in vacuo to yield a residue that was purified using flash chromatography (Biotage SP4 12 g cartridge; 0-10% MeOH gradient in CH2Cl2) to give a mixture of products containing the desired product. The mixture was further purified using flash chromatography (Biotage SP4, 12 g cartridge, C18 phase, 20-40% acetonitrile gradient in water) to give 4-{1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-5-oxo-2,3-dihydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-10a(10H)-yl}benzonitrile (37) as a white solid (13 mg, yield 42%).

Workup

  1. waitfollowed by 2 h at room temperature
  2. concentrationThe resulting solution was concentrated in vacuo
  3. customto give a brown oil that
  4. concentrationconcentrated in vacuo
  5. temperatureTo a chilled
  6. temperatureThe brown reaction mixture was warmed to room temperature
  7. stirringstirred for a further 64 h
  8. extractionthe mixture extracted with CH2Cl2 (3×25 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. customto yield a residue that
  12. customwas purified
  13. customto give
  14. additiona mixture of products

Sources & evidence

ORD record
ord-f8ae47a6139d4a4a8daa025525593cd1
Source dataset
uspto-grants-2015_10
Patent number
US09163029B2

Reaction notes

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