Hydrochloric Acid → 3-[1-(3-Hydroxypropyl)-1h-indol-3-yl]-4-(1h-indol-7-yl)-pyrrole-2,5-dione

HRID 2215776Notes

Reaction equation

HRID 2215776 reaction equation
CC([O-])(C)C.[K+].C1COCC1.[OH:12][CH2:13][CH2:14][CH2:15][N:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]([CH2:25][C:26]([NH2:28])=[O:27])=[CH:17]1.C[O:30][C:31](=O)[C:32]([C:34]1[CH:35]=[CH:36][CH:37]=[C:38]2[C:42]=1[N:41](COCC[Si](C)(C)C)[CH:40]=[CH:39]2)=O.Cl>CN(C=O)C.CCOC(C)=O>[OH:12][CH2:13][CH2:14][CH2:15][N:16]1[C:24]2[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=2)[C:18]([C:25]2[C:26](=[O:27])[NH:28][C:31](=[O:30])[C:32]=2[C:34]2[CH:35]=[CH:36][CH:37]=[C:38]3[C:42]=2[NH:41][CH:40]=[CH:39]3)=[CH:17]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 106572082-[1-(3-hydroxypropyl)-1H-indol-3-yl]acetamideHCID 23665647Potassium tert-butoxideHCID 69641843{1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-7-yl}-oxo-acetic acid methyl ester

Product 1

HCID 219499853-[1-(3-Hydroxypropyl)-1h-indol-3-yl]-4-(1h-indol-7-yl)-pyrrole-2,5-dioneYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 1.0 M solution of KOtBu in THF (8.1 mL, 8.1 mmol) was added to a solution of 2-(1-3-hydroxypropyl-1H-indol-3-yl)-acetamide (586 mg, 2.52 mmol) and {1-(2-trimethylsilanyl-ethoxymethyl)-1H-indol-7-yl}-oxo-acetic acid methyl ester (770 mg, 2.31 mmol) in DMF (30 mL). The initially clear orange-red solution turned deep red over 15 min, and was then heated to 65 C. for 18 h. 1N HCl was added, the mixture stirred 8 h and then the volume was reduced to ˜20 mL. The residue was poured into EtOAc/0.1 N HCl and the aqueous layer was separated and extracted with EtOAc. The EtOAc solutions were combined and washed with water, saturated aq NaHCO3 and brine (3×), dried (MgSO4), filtered and concentrated onto SiO2. Flash chromatography (8:2 EtOAc:hexanes) afforded a red solid that was dried at 75° C. for overnight giving the title compound (454 mg, 51%) as a bright red solid. 1H NMR (400 MHz, DMSO-d6) 11.04 (s, 1H), 10.71 (s, 1H), 8.03 (s, 1H), 7.56–7.62 (m, 1H), 7.41 (d, J=8 Hz, 1H), 7.20 (dd, J=3, 3 Hz, 1H), 6.94–7.0 (m, 3H), 6.45 (dd, J=8, 8 Hz, 1H), 6.40–6.43 (m, 1H), 6.11 (d, J=8 Hz, 1H), 4.64 (t, J=5 Hz, 1H), 4.29 (t, J=7 Hz, 2H), 3.38 (s, 2H), 1.88 (m, 2H). MS (electrospray, m/z) 386.2 (M++1), 384.2 (M−−1). HRMS 386.1504 (M++1, calcd for C23H20N3O3 386.1505)

Workup

  1. temperaturewas then heated to 65 C
  2. waitfor 18 h
  3. customthe aqueous layer was separated
  4. extractionextracted with EtOAc
  5. washwashed with water, saturated aq NaHCO3 and brine (3×)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated onto SiO2
  9. customFlash chromatography (8:2 EtOAc:hexanes) afforded a red solid that
  10. customwas dried at 75° C. for overnight

Sources & evidence

ORD record
ord-2ef73b7c7f1b49d28092c72cbfe07c8f
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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