2-(1-Methyl-1H-indol-3-YL)-2-oxoacetic acid methyl ester → 3-[3-(4,7-Diaza-spiro[2.5]oct-7-yl)-naphthalen-1-yl]-4-(1-methyl-1H-indol-3-yl)-pyrrole-2,5-dione

HRID 900145Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 900145
[CH2:1]1[C:3]2([CH2:8][N:7]([C:9]3[CH:10]=[C:11]([CH2:19][C:20]([NH2:22])=[O:21])[C:12]4[C:17]([CH:18]=3)=[CH:16][CH:15]=[CH:14][CH:13]=4)[CH2:6][CH2:5][NH:4]2)[CH2:2]1.C[O:24][C:25](=O)[C:26]([C:28]1[C:36]2[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=2)[N:30]([CH3:37])[CH:29]=1)=O.CC([O-])(C)C.[K+]>C1COCC1>[CH2:2]1[C:3]2([CH2:8][N:7]([C:9]3[CH:10]=[C:11]([C:19]4[C:20](=[O:21])[NH:22][C:25](=[O:24])[C:26]=4[C:28]4[C:36]5[C:31](=[CH:32][CH:33]=[CH:34][CH:35]=5)[N:30]([CH3:37])[CH:29]=4)[C:12]4[C:17]([CH:18]=3)=[CH:16][CH:15]=[CH:14][CH:13]=4)[CH2:6][CH2:5][NH:4]2)[CH2:1]1

Komponenten

5

Edukt 3

HCID 44536752-(1-Methyl-1H-indol-3-YL)-2-oxoacetic acid methyl esterHCID 211145032-[3-(4,7-Diaza-spiro[2.5]oct-7-yl)-naphthalen-1-yl]-acetamideHCID 23665647Potassium tert-butoxide

Produkt 1

HCID 211145053-[3-(4,7-Diaza-spiro[2.5]oct-7-yl)-naphthalen-1-yl]-4-(1-methyl-1H-indol-3-yl)-pyrrole-2,5-dione

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel3×

Versuchsvorschrift

2-[3-(4,7-Diaza-spiro[2.5] oct-7-yl)-naphthalen-1-yl]-acetamide (100 mg, 0.30 mmol) and (1-methyl-1H-indol-3-yl)-oxo-acetic acid methyl ester (97 mg, 0.44 mmol) are azeotroped three times with dry THF and then dissolved in dry THF (3 ml). A solution of 1.0 M KOtBu in THF (1.2 ml) is added dropwise over 20 minutes at RT. After 5 minutes, TLC analysis indicates complete conversion of starting materials. The reaction is quenched by the additon of water (5 ml). The mixture is diluted with EtOAc and washed twice with saturated aq. NH4Cl. The aqueous layers are back extracted twice with EtOAc. The combined organic layers are dried over Na2SO4 and the solvent is evaporated. The residue is purified by FCC (EtOAc/AcOH/H2O 800:55:45) to afford the title compound as its acetate salt. The compound is dissolved in MeOH/TFA and the solvent is removed to yield the title compound as its trifluoroacetate salt. 1H NMR (DMSO, 400 MHz) δ 0.95 (M, 4H), 3.39 (br, 4H), 3.49 (br, 2H), 3.86 (s, 3H), 6.16 (d, J=7.9 Hz, 1H), 6.46 (dd, J=6.6/7.9 Hz, 1H), 7.00 (dd, J=6.6/7.9 Hz, 1H), 7.13 (dd, J=7.6/7.6 Hz, 1H), 7.40 (m, 4H), 7.55 (d, J=8.5 Hz, 1 H), 7.78 (d, J=7.6 Hz, 1H), 8.14 (s, 1H), 9.10 (br, 2H), 11.17 (s, 1H); ES-MS: 463 [M+H]+.

Aufarbeitung

  1. customThe reaction is quenched by the additon of water (5 ml)
  2. additionThe mixture is diluted with EtOAc
  3. washwashed twice with saturated aq. NH4Cl
  4. extractionThe aqueous layers are back extracted twice with EtOAc
  5. dry with materialThe combined organic layers are dried over Na2SO4
  6. customthe solvent is evaporated
  7. customThe residue is purified by FCC (EtOAc/AcOH/H2O 800:55:45)

Quellen und Nachweise

ORD-Eintrag
ord-d742cfbbd7a1481d96fe110deeb3f771
Quelldatensatz
uspto-grants-2008_04
Patentnummer
US07358253B2

Notizen zur Reaktion

Wird geladen…