P-Toluic Acid → HCID 54306168, compound

HRID 1934817Notes

Reaction equation

HRID 1934817 reaction equation
[CH3:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][CH:3]=1.[C:11](N1C=CN=C1)(N1C=CN=C1)=O.[NH2:23][C@H:24]1[CH2:29][C:28]2[C:30]([N:35]3[CH2:40][CH2:39][NH:38][CH2:37][CH:36]3C)=[CH:31][CH:32]=[C:33]([CH3:34])[C:27]=2[O:26][CH2:25]1>CN(C)C=O>[CH3:34][C:33]1[C:27]2[O:26][CH2:25][C@@H:24]([NH:23][C:6](=[O:8])[C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:10][CH:9]=3)[CH2:29][C:28]=2[C:30]([N:35]2[CH2:40][CH2:39][N:38]([CH3:11])[CH2:37][CH2:36]2)=[CH:31][CH:32]=1

Participants

5

Reactant 3

HCID 7470P-Toluic AcidHCID 682631,1'-CarbonyldiimidazoleHCID 69941088HCID 69941088, compound

Product 1

HCID 54306168HCID 54306168, compoundYield 40.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
75 °C

Procedure

4-Methylbenzoic acid (22 mg, 0.16 mmol) and 1,1′-carbonyldiimidazole (27 mg, 0.17 mmol) were dissolved in dry N,N-dimethylformamide (2 mL) and stirred at 75° C. for 1 h. The reaction mixture was cooled to room temperature and a solution of (S)-3-amino-8-methyl-5-(methylpiperazin-1-yl)-3,4-dihydro-2H-1-benzopyran (40 mg, 0.15 mmol) dissolved in dry N,N-dimethylformamide (4 mL) was added. The reaction mixture was stirred at room temperature for 4 days and the solvent was evaporated in vactio. The crude material was partitioned between methylene chloride (40 mL) and water (10 mL). The organic phase was washed with water (10 mL) and brine (5 mL) and dried (MgSO4). The solvent was evaporated in vacuo giving 48 mg of a crude product. Purification by preparative TLC on silica using chloroform/ethanol (saturated with ammonia) (15:1) as the eluent afforded 23 mg (40% yield) of the title compound as a white solid: mp 191-192° C.; EIMS (70 eV) m/z (relative intensity) 379 (100, M+); [α]21D−7° (c 0.10, chloroform).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. additionwas added
  3. stirringThe reaction mixture was stirred at room temperature for 4 days
  4. customthe solvent was evaporated in vactio
  5. customThe crude material was partitioned between methylene chloride (40 mL) and water (10 mL)
  6. washThe organic phase was washed with water (10 mL) and brine (5 mL)
  7. dry with materialdried (MgSO4)
  8. customThe solvent was evaporated in vacuo
  9. customgiving 48 mg of a crude product
  10. customPurification by preparative TLC on silica

Sources & evidence

ORD record
ord-153d00c61f274dea80a0e5dc1b65d1d7
Source dataset
uspto-grants-2002_05
Patent number
US06384225B1

Reaction notes

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