Dimethylformamide → HCID 58406390, compound

HRID 1753146Notes

Reaction equation

HRID 1753146 reaction equation
CN(C=O)C.[CH3:6][C:7]1[O:11][N:10]=[CH:9][C:8]=1[C:12]([OH:14])=O.[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]23[NH:40][CH2:39][CH2:38][N:23]2[C:24](=[O:37])[C:25]2[N:26]([C:28]([C:31]4[CH:36]=[CH:35][N:34]=[CH:33][CH:32]=4)=[CH:29][CH:30]=2)[CH2:27]3)=[CH:18][CH:17]=1.C(#N)C>ClCCl.N1C=CC=CC=1.C([O-])(O)=O.[Na+].O>[Cl:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]23[N:40]([C:12]([C:8]4[CH:9]=[N:10][O:11][C:7]=4[CH3:6])=[O:14])[CH2:39][CH2:38][N:23]2[C:24](=[O:37])[C:25]2[N:26]([C:28]([C:31]4[CH:32]=[CH:33][N:34]=[CH:35][CH:36]=4)=[CH:29][CH:30]=2)[CH2:27]3)=[CH:18][CH:17]=1

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 6342AcetonitrileHCID 14252405-Methylisoxazole-4-carboxylic acidHCID 67367651HCID 67367651, compound

Product 1

HCID 58406390HCID 58406390, compoundYield 12%

Reagents, catalysts & solvents 4

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

Conditions

Temperature
0 °C

Procedure

To generate the acid chloride oxalyl chloride (100 μL, 1.2 mmol) and a drop of DMF were added to a suspension of 5-methyl-1,2-oxazole-4-carboxylic acid (76 mg, 0.60 mmol) in dichloromethane (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 dark 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; 0.60 mmol) in pyridine (0.5 mL) and CH2Cl2 (0.5 mL) was added crude 10a-(4-chlorophenyl)-8-(pyridin-4-yl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (50 mg, 0.14 mmol) in pyridine (0.5 mL). The dark reaction mixture was warmed to room temperature and stirred for a further 16 h. LCMS analysis confirmed completion of the reaction. The reaction mixture was diluted with a saturated 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 crude brown solid, which was purified using 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)-1-[(5-methyl-1,2-oxazol-4-yl)carbonyl]-8-(pyridin-4-yl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (32) as a white solid (7 mg, yield 12%).

Workup

  1. waitfollowed by 2 h at room temperature
  2. concentrationThe resulting solution was concentrated in vacuo
  3. customto give a dark oil that
  4. concentrationconcentrated in vacuo
  5. temperatureTo a chilled
  6. customThe dark reaction mixture
  7. temperaturewas warmed to room temperature
  8. stirringstirred for a further 16 h
  9. customcompletion of the reaction
  10. extractionextracted with CH2Cl2 containing 20% of propan-2-ol (3×25 mL)
  11. dry with materialdried (MgSO4)
  12. concentrationconcentrated in vacuo
  13. customto yield a crude brown solid, which
  14. customwas purified

Sources & evidence

ORD record
ord-a0d3e814725347989cf27997c4b1ae8a
Source dataset
uspto-grants-2015_10
Patent number
US09163029B2

Reaction notes

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