Acetonitrile → HCID 58406426, compound

HRID 1910932Notes

Reaction equation

HRID 1910932 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.[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]23[NH:40][CH2:39][CH2:38][N:24]2[C:25](=[O:37])[C:26]2[N:27]([CH:29]=[C:30]([C:32]([N:34]([CH3:36])[CH3:35])=[O:33])[CH:31]=2)[CH2:28]3)=[CH:19][CH:18]=1.C(#N)C>CN(C=O)C.C(Cl)Cl.N1C=CC=CC=1.C([O-])(O)=O.[Na+].O>[Cl:16][C:17]1[CH:22]=[CH:21][C:20]([C:23]23[N:40]([C:13]([C:12]4[C:8]([CH3:7])=[N:9][O:10][CH:11]=4)=[O:15])[CH2:39][CH2:38][N:24]2[C:25](=[O:37])[C:26]2[N:27]([CH:29]=[C:30]([C:32]([N:34]([CH3:36])[CH3:35])=[O:33])[CH:31]=2)[CH2:28]3)=[CH:19][CH:18]=1

Participants

10

Reactant 4

HCID 6342AcetonitrileHCID 65578Oxalyl chlorideHCID 45896923-Methyl-1,2-oxazole-4-carboxylic acidHCID 67370984HCID 67370984, compound

Product 1

HCID 58406426HCID 58406426, compoundYield 20.7%

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 1049PyridineSolvent2×HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °C

Procedure

To generate the acid chloride, oxalyl chloride (45 μL, 0.54 mmol) and DMF (1 drop) were added to a suspension of 3-methyl-1,2-oxazole-4-carboxylic acid (35 mg, 0.28 mmol) in CH2Cl2 (0.5 mL) at 0° C. The suspension was allowed to stir for a further 15 min at 0° C., followed by 2 h at room temperature. The resulting solution was concentrated in vacuo to give a oil that was twice suspended in n-hexanes (2×1 mL) and concentrated in vacuo. To a chilled (ice bath) suspension of the acid chloride (generated as above; 0.28 mmol) in pyridine (0.5 mL) and CH2Cl2 (0.5 mL) was added 10a-(4-chlorophenyl)-N,N-dimethyl-5-oxo-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazine-7-carboxamide (12 mg, 33 μmol) in pyridine (0.5 mL). The brown reaction mixture was warmed to room temperature and stirred for 16 h (monitored by LCMS). The reaction mixture was diluted with saturated aqueous solution of NaHCO3 (25 mL) and extracted with CH2Cl2 containing 20% of propan-2-ol (3×25 mL). The organic fractions were combined, dried (MgSO4) and concentrated in vacuo to yield a residue that was purified by flash chromatography (Biotage SP4, 12 g cartridge; 0-10% MeOH gradient in CH2Cl2) and reverse phase chromatography (Biotage SP4, 12 g cartridge, C18 phase; 20-40% acetonitrile gradient in water) to give 10a-(4-chlorophenyl)-N,N-dimethyl-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-7-carboxamide (38) as a white solid (3.2 mg, yield 20%).

Workup

  1. waitfollowed by 2 h at room temperature
  2. concentrationThe resulting solution was concentrated in vacuo
  3. customto give a oil that
  4. concentrationconcentrated in vacuo
  5. temperatureTo a chilled
  6. temperatureThe brown reaction mixture was warmed to room temperature
  7. stirringstirred for 16 h (monitored by LCMS)
  8. extractionextracted with CH2Cl2 containing 20% of propan-2-ol (3×25 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. customto yield a residue that
  12. customwas purified by flash chromatography (Biotage SP4, 12 g cartridge; 0-10% MeOH gradient in CH2Cl2)

Sources & evidence

ORD record
ord-54f95438d64547228b8e02a687860e07
Source dataset
uspto-grants-2013_12
Patent number
US08604034B2

Reaction notes

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