HCID 67994842, compound → HCID 67994884, compound

HRID 2361429Notes

Reaction equation

HRID 2361429 reaction equation
[CH3:1][C:2]1[C:7]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[CH:9]2)=[CH:6][CH:5]=[CH:4][C:3]=1[C:19]1[CH:27]=[CH:26][C:25]([C:28]([NH2:30])=[O:29])=[C:24]2[C:20]=1[C:21]1[CH2:34][NH:33][CH2:32][CH2:31][C:22]=1[NH:23]2>C(OCCCC)(=O)C.CO.[O-2].[O-2].[Mn+4]>[CH3:1][C:2]1[C:7]([N:8]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=[CH:9]2)=[CH:6][CH:5]=[CH:4][C:3]=1[C:19]1[CH:27]=[CH:26][C:25]([C:28]([NH2:30])=[O:29])=[C:24]2[C:20]=1[C:21]1[CH:34]=[N:33][CH:32]=[CH:31][C:22]=1[NH:23]2

Participants

5

Reactant 1

HCID 67994842HCID 67994842, compound

Product 1

HCID 67994884HCID 67994884, compoundYield 35.7%

Reagents, catalysts & solvents 3

HCID 178418406HCID 178418406, compoundCatalystHCID 887MethanolSolventHCID 31272Butyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 9-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-6-carboxamide (10 mg, 0.022 mmol) and activated manganese dioxide (19.34 mg, 0.222 mmol) in butyl acetate (0.5 mL) was heated on an oil bath at 110° C. for 5.25 h, then at 90-100° C. for 2.5 days, then at 125° C. for 20 h. The mixture was cooled to room temperature, diluted with methanol, filtered and concentrated under vacuum. The residue was purified by preparative HPLC. The effluent containing the desired product was concentrated under vacuum to provide a fine aqueous suspension. This was extracted three times with EtOAc, and the combined organic phases were dried and concentrated to provide the desired product as an off-white solid (3.5 mg, 33% yield). LCMS (M+H)+ m/z 446.2. 1H NMR (400 MHz, methanol-d4) δ 8.31-8.47 (3.6 H, m), 8.06-8.16 (1.4 H, m), 7.87-7.96 (1 H, m), 7.76-7.87 (1 H, m), 7.55-7.70 (5 H, m), 7.24-7.36 (1 H, m), 1.90 (3 H, 2s).

Workup

  1. waitat 125° C. for 20 h
  2. temperatureThe mixture was cooled to room temperature
  3. filtrationfiltered
  4. concentrationconcentrated under vacuum
  5. customThe residue was purified by preparative HPLC
  6. additionThe effluent containing the desired product
  7. concentrationwas concentrated under vacuum
  8. customto provide a fine aqueous suspension
  9. extractionThis was extracted three times with EtOAc
  10. customthe combined organic phases were dried
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-17b607fc6dd746068c307e629c64d025
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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