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

HRID 2215767Notes

Reaction equation

HRID 2215767 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]([CH3:43])[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[N:41]([CH3:43])[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 69642215(1-Methyl-1H-indol-7-yl)-oxo-acetic acid methyl ester

Product 1

HCID 219500353-[1-(3-Hydroxypropyl)-1H-indol-3-yl]-4-(1-methyl-1H-indol-7-yl)-pyrrole-2,5-dioneYield 66.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 1.0 M solution of KOtBu in THF (9.2 mL, 9.2 mmol) was added to a solution of 2-(1-3-hydroxypropyl-1H-indol-3-yl)-acetamide (616 mg, 2.65 mmol) and (1-methyl-1H-indol-7-yl)-oxo-acetic acid methyl ester (566 mg, 2.61 mmol) in DMF (40 mL). The initially light yellow solution turned red-orange and was stirred 14 h at rt. 1N HCl was added and the mixture poured into EtOAc. The EtOAc layer was separated and washed with water (3×), saturated aq NaHCO3 (2×) and brine (3×), dried (MgSO4), filtered and concentrated onto SiO2. Flash chromatography (1:1 EtOAc:CH2Cl2) afforded a red solid that was dried at 70° C. for 72 h giving the title compound (689 mg, 66%) as a bright red solid. 1H NMR (400 MHz, DMSO-d6) 11.12 (s, 1H), 8.05 (s, 1H), 7.61 (d, J=8 Hz, 1H), 7.43 (d, J=8 Hz, 1H), 7.25 (d, J=3 Hz, 1H), 6.92–7.04 (m, 2H), 6.87 (d, J=8 Hz, 1H), 6.44–6.50 (m, 2H), 6.21 (d, J=8 Hz, 1H), 4.64 (m, 1H), 4.27 (t, J=7 Hz, 2H), 3.68 (s, 3H), 3.30–3.40 (m, 2H), 1.80–1.90 (m, 2H). 13C NMR (75.5 MHz, DMSO-d6) 173.43, 172.37, 136.15, 134.62, 134.26, 131.54, 129.58, 129.19, 128.57, 125.20, 124.11, 122.07, 121.53, 121.03, 120.12, 118.56, 115.18, 110.34, 104.28, 100.73, 57.54, 42.94, 34.68, 32.54. IR (CHCl3, cm−1) 3436, 1721. MS (electrospray, m/z) 400 (M++1), 398 (M−−1). Anal. Calcd for C24H21N3O3: C, 72.17; H, 5.30; N, 10.52. Found: C, 71.87; H, 5.29; N, 10.45.

Workup

  1. customThe EtOAc layer was separated
  2. washwashed with water (3×), saturated aq NaHCO3 (2×) and brine (3×)
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated onto SiO2
  6. customFlash chromatography (1:1 EtOAc:CH2Cl2) afforded a red solid that
  7. customwas dried at 70° C. for 72 h

Sources & evidence

ORD record
ord-8168a3961ec24fa884e44c4144623e39
Source dataset
uspto-grants-2006_09
Patent number
US07109229B2

Reaction notes

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