Acetic Acid → HCID 59408993, compound

HRID 1894736Notes

Reaction equation

HRID 1894736 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C:12]([NH2:14])=[O:13].C[O:16][C:17](=O)[C:18](=O)[C:19]1[CH:20]=[C:21]2[C:26]3=[C:27]([CH2:29][CH2:30][N:25]3[CH2:24][CH2:23][CH2:22]2)[CH:28]=1.CC(C)([O-])C.[K+].N1CCCCC1.C(O)(=O)C>O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[C:11]1[C:12](=[O:13])[NH:14][C:17](=[O:16])[C:18]=1[C:19]1[CH:20]=[C:21]2[C:26]3=[C:27]([CH2:29][CH2:30][N:25]3[CH2:24][CH2:23][CH2:22]2)[CH:28]=1

Participants

7

Reactant 5

HCID 176Acetic AcidHCID 8082PiperidineHCID 2588132-(5-bromo-1H-indol-3-yl)acetamideHCID 23665647Potassium tert-butoxideHCID 59408989HCID 59408989, compound

Product 1

HCID 59408993HCID 59408993, compoundYield 46%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 2-(5-bromo-1H-indol-3-yl)-acetamide (500 mg, 1.98 mmol) and oxo-(1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-8-yl)-acetic acid methyl ester (404 mg, 1.65 mmol) in anhydrous tetrahydrofuran at 0° C. was added a solution of potassium tert-butoxide (4.95 ml, 4.95 mmol; 1M solution in tetrahydrofuran) dropwise over 5 minutes. The reaction was stirred for a further 30 minutes then cooled to 0° C. and quenched with water (50 ml) and acidified to pH6 with aqueous 2M hydrochloric acid. The mixture was extracted with dichloromethane (3×50 ml) and the combined organic extracts were dried over anhydrous sodium sulfate and evaporated to dryness. The residue was dissolved in N,N-dimethylformamide (4 ml) and treated with piperidine (99 μl, 1.00 mmol) and acetic acid (57 μl, 1.00 mmol). The mixture was heated to 150° C. for 5 minutes under microwave conditions then partitioned between ethyl acetate (50 ml) and water (30 ml). The aqueous layer was removed and the organic layer was washed with water (2×30 ml). The organic layer was dried over anhydrous sodium sulfate and evaporated to dryness. The residue was purified by flash column chromatography (SiO2, 1% methanol to 10% methanol in dichloromethane) to provide 3-(5-bromo-1H-indol-3-yl)-4-(1,2,5,6-tetrahydro-4H-pyrrolo[3,2,1-ij]quinolin-8-yl)-pyrrole-2,5-dione as a red solid (340 mg). 400 MHz 1H NMR (CDCl3) δ: 8.71 (s, 1H), 7.96 (d, J=2.4 Hz, 1H), 7.48 (s, 1H), 7.27 (m, 2H), 7.08 (s, 1H), 6.94 (s, 1H), 6.56 (s, 1H), 3.36 (t, J=8.0 Hz, 2H), 3.07 (m, 2H), 3.83 (t, J=8.0 Hz, 2H), 2.47 (t, J=6.8 Hz, 2H), 2.04 (m, 2H); LCMS: 448 and 450 [M+H].

Workup

  1. customquenched with water (50 ml)
  2. extractionThe mixture was extracted with dichloromethane (3×50 ml)
  3. dry with materialthe combined organic extracts were dried over anhydrous sodium sulfate
  4. customevaporated to dryness
  5. dissolutionThe residue was dissolved in N,N-dimethylformamide (4 ml)
  6. temperatureThe mixture was heated to 150° C. for 5 minutes under microwave conditions
  7. customthen partitioned between ethyl acetate (50 ml) and water (30 ml)
  8. customThe aqueous layer was removed
  9. washthe organic layer was washed with water (2×30 ml)
  10. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  11. customevaporated to dryness
  12. customThe residue was purified by flash column chromatography (SiO2, 1% methanol to 10% methanol in dichloromethane)

Sources & evidence

ORD record
ord-95119f1ee8174fb0919d90d4fff57822
Source dataset
uspto-grants-2013_08
Patent number
US08513292B2

Reaction notes

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