Hydrochloric Acid → HCID 67980614, compound

HRID 1260161Notes

Reaction equation

HRID 1260161 reaction equation
CO[C:3](=[O:22])[C:4]([C:6]1[C:16]2=[C:17]3[C:12](=[CH:13][CH:14]=[CH:15]2)C(OC(=O)C)CC[N:8]3[CH:7]=1)=O.[NH:23]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25]([CH2:32][C:33]([NH2:35])=[O:34])=[CH:24]1.CC(C)([O-])C.[K+].Cl.[O:43]1C[CH2:46][CH2:45][CH2:44]1>O>[OH:43][CH:44]1[C:16]2[C:17]3=[C:12]([C:6]([C:4]4[C:3](=[O:22])[NH:35][C:33](=[O:34])[C:32]=4[C:25]4[C:26]5[C:31](=[CH:30][CH:29]=[CH:28][CH:27]=5)[NH:23][CH:24]=4)=[CH:7][N:8]3[CH2:46][CH2:45]1)[CH:13]=[CH:14][CH:15]=2

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 397Indole-3-acetamideHCID 8028TetrahydrofuranHCID 23665647Potassium tert-butoxideHCID 67980763HCID 67980763, compound

Product 1

HCID 67980614HCID 67980614, compoundYield 36%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of methyl[6-(acetyloxy)-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl](oxo)acetate (632 mg, 2.09 mmol) and indole-3-acetamide (328 mg, 1.88 mmol) in anhydrous tetrahyrofuran (25 mL) at 0° C. was added a solution of potassium tert-butoxide (9.3 mL, 9.3 mmol, 1M in THF) dropwise over 30 min. The mixture was stirred at 0° C., allowed to warm to room temperature and stirred for 2 h. Concentrated hydrochloric acid (1 mL) was added and the mixture stirred for 1 hour at room temperature. The mixture was diluted with water (25 mL), and extracted with ethyl acetate (2×25 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution (50 mL) and dried over anhydrous sodium sulfate. The residue was purified by silica gel chromatography, eluting with a methanol/dichloromethane (1-5%) to afford 3-(6-hydroxy-5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-(1H-indol-3-yl)-1H-pyrrole-2,5-dione as a bright red solid (293 mg, 36%). Mp: 165-168° C.; 1H NMR (DMSO-d6) 400 MHz δ: 11.62 (brs, 1H), 10.89 (brs, 1H), 7.85 (s, 1H), 7.65 (s, 1H), 7.38 (d, J=8.2 Hz, 1H), 6.96-6.94 (m, 3H), 6.71 (t, J=7.4 Hz, 1H), 6.59 (d, J=7.4 Hz, 1H), 6.49 (d, J=8.2 Hz, 1H), 5.41 (d, J=5.0 Hz, 1H), 4.89 (brs, 1H), 4.26 (s, 2H), 3.33 (s, 2H); LCMS [M+H]: 384.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 2 h
  3. stirringthe mixture stirred for 1 hour at room temperature
  4. extractionextracted with ethyl acetate (2×25 mL)
  5. washThe combined organic layers were washed with saturated aqueous sodium chloride solution (50 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with a methanol/dichloromethane (1-5%)

Sources & evidence

ORD record
ord-f16064d885714da8bcb5404aee1df925
Source dataset
uspto-grants-2013_06
Patent number
US08470786B2

Reaction notes

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