Formamide → 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 900146Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 900146
C(O[C:4](=[O:31])[CH2:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]=[C:8]([N:16]2[CH2:23][C:20]3([CH2:22][CH2:21]3)[N:19](CC3C=CC=CC=3)[CH2:18][CH2:17]2)[CH:7]=1)C.C(N1CCN(C2[CH:48]=[C:49]([CH2:57][C:58]([NH2:60])=[O:59])[C:50]3[C:55](C=2)=[CH:54][CH:53]=[CH:52][CH:51]=3)CC21CC2)C1C=CC=CC=1.[CH:61]([NH2:63])=O.C[O-].[Na+]>CN(C=O)C.CO>[CH2:21]1[C:20]2([CH2:23][N:16]([C:8]3[CH:7]=[C:6]([C:5]4[C:4](=[O:31])[NH:60][C:58](=[O:59])[C:57]=4[C:49]4[C:50]5[C:55](=[CH:54][CH:53]=[CH:52][CH:51]=5)[N:63]([CH3:61])[CH:48]=4)[C:15]4[C:10]([CH:9]=3)=[CH:11][CH:12]=[CH:13][CH:14]=4)[CH2:17][CH2:18][NH:19]2)[CH2:22]1

Komponenten

6

Edukt 3

HCID 713FormamideHCID 10942334Sodium MethoxideHCID 865983552-[3-(4-Benzyl-4,7-diaza-spiro[2.5] oct-7-yl)-naphthalen-1-yl]-acetamide [3-(4-Benzyl-4,7-diaza-spiro[2.5] oct-7-yl)-naphthalen-1-yl]-acetic acid ethyl ester

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 2

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
105 °C

Versuchsvorschrift

2-[3-(4-Benzyl-4,7-diaza-spiro[2.5] oct-7-yl)-naphthalen-1-yl]-acetamide [3-(4-Benzyl-4,7-diaza-spiro[2.5] oct-7-yl)-naphthalen-1-yl]-acetic acid ethyl ester (347 mg, 0.84 mmol) and formamide (126 mg, 2.80 mmol) are dissolved under an atmosphere of argon in DMF (1 ml). The solution is heated to 105° C., and NaOMe (155 μL of a 5.4 M solution in MeOH, 45 mg, 0.84 mmol) is added dropwise during 15 minutes. After 30 minutes at 105° C., TLC analysis indicates complete consumption of starting material. The reaction mixture is cooled to RT, diluted with water, and extracted with EtOAc. The EtOAc layers are washed twice with water. Removal of solvent and purification by FCC (EtOAc/MeOH 98:2 to 96:4 to 90:10) yielded the title compound. 1H NMR (CDCl3, 400 MHz) δ 0.71 (ddd, 2H), 0.89 (ddd, 2H), 3.10 (ddd, 2H), 3.16 (s, 2H), 3.31 (ddd, 2H), 3.93 (s, 2H), 3.99 (s, 2H), 3.99 (s, 2H), 5.33 (br, 1H), 5.42 (br, 1H), 7.11 (s, 1H), 7.23 (d, J=2.0, 1H), 7.32 (m, 5H), 7.37 (dd, J=6.7 Hz, 1H), 7.45 (dd, J=6.7 Hz, 1H), 7.73 (d, J=8.9 Hz, 1H), 7.85 (d, J=8.9 Hz, 1H); ES-MS: 386 [M+H]+.

Aufarbeitung

  1. customconsumption of starting material
  2. temperatureThe reaction mixture is cooled to RT
  3. additiondiluted with water
  4. extractionextracted with EtOAc
  5. washThe EtOAc layers are washed twice with water
  6. customRemoval of solvent and purification by FCC (EtOAc/MeOH 98:2 to 96:4 to 90:10)

Quellen und Nachweise

ORD-Eintrag
ord-39ac8e06d0b0454ab483a6297860538b
Quelldatensatz
uspto-grants-2008_04
Patentnummer
US07358253B2

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