Acetic Anhydride → HCID 67994868, compound

HRID 2361426Notes

Reaction equation

HRID 2361426 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:35](OC(=O)C)(=[O:37])[CH3:36]>C1COCC1>[C:35]([N:33]1[CH2:32][CH2:31][C:22]2[NH:23][C:24]3[C:20]([C:21]=2[CH2:34]1)=[C:19]([C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([N:8]2[C:17](=[O:18])[C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[N:10]=[CH:9]2)[C:2]=1[CH3:1])[CH:27]=[CH:26][C:25]=3[C:28]([NH2:30])=[O:29])(=[O:37])[CH3:36]

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 67994842HCID 67994842, compound

Product 1

HCID 67994868HCID 67994868, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A cloudy solution of 9-(2-methyl-3-(4-oxoquinazolin-3(4H)-yl)phenyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-6-carboxamide (20 mg, 0.044 mmol) in THF (0.5 mL) was treated with TEA (0.019 mL, 0.133 mmol) and stirred on an ice-water bath. The mixture was treated with acetic anhydride (nominally 8.40 μl, 0.089 mmol, probably more was added) and the resulting clear solution was stirred at room temperature for 1.5 h. The mixture was concentrated under vacuum, and the residue was purified by preparative HPLC. Effluent fractions containing the desired product were treated with NaHCO3 (aq) and concentrated under vacuum. The resulting aqueous suspension was filtered and the precipitate was washed with water and dried under vacuum to provide the desired product as a white solid (7.0 mg). The filter and aqueous phase were extracted three times with EtOAc, and the organic extracts were dried and concentrated to provide additional desired product as a white solid (1.5 mg) for a total of 8.5 mg (39% yield). LCMS (M+H)+ m/z 492.2, (M+Na)+514.2. 1H NMR (400 MHz, methanol-d4) δ 8.30-8.55 (2 H, m), 7.87-7.97 (1 H, m), 7.83 (1 H, t, J=7.9 Hz), 7.70 (1 H, dd, J=7.7, 1.3 Hz), 7.61-7.68 (1 H, m), 7.44-7.59 (3 H, m), 6.90-7.05 (1 H, m), 3.58-4.61 (4 H, m), 2.86-3.08 (2 H, m), 1.80-2.21 (6 H, multiple singlets).

Workup

  1. additionprobably more was added) and the resulting clear solution
  2. stirringwas stirred at room temperature for 1.5 h
  3. concentrationThe mixture was concentrated under vacuum
  4. customthe residue was purified by preparative HPLC
  5. additionEffluent fractions containing the desired product
  6. additionwere treated with NaHCO3 (aq)
  7. concentrationconcentrated under vacuum
  8. filtrationThe resulting aqueous suspension was filtered
  9. washthe precipitate was washed with water
  10. customdried under vacuum

Sources & evidence

ORD record
ord-9f169112616f4124aa0f34228f84de50
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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