Diisopropylethylamine → (3R*,4S*)-4-carbomethoxymethyl-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril

HRID 11604

Reaktionsgleichung

Reaktionsgleichung von HRID 11604
FC(F)(F)C(O)=O.[NH2:8][C@H:9]1[C@H:18]([CH2:19][C:20]([O:22][CH3:23])=[O:21])[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:11][C:10]1=[O:24].Cl.CN(C)CCCN=C=NCC.ON1C2N=CC=CC=2N=N1.[Cl:47][C:48]1[CH:49]=[C:50]2[C:54](=[CH:55][CH:56]=1)[NH:53][C:52]([C:57](O)=[O:58])=[CH:51]2.C(N(C(C)C)CC)(C)C>O.CO.CN(C)C=O>[C:20]([CH2:19][C@H:18]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[NH:11][C:10](=[O:24])[C@@H:9]1[NH:8][C:57]([C:52]1[NH:53][C:54]2[C:50]([CH:51]=1)=[CH:49][C:48]([Cl:47])=[CH:56][CH:55]=2)=[O:58])([O:22][CH3:23])=[O:21]

Komponenten

9

Edukt 5

HCID 81531DiisopropylethylamineHCID 826935-Chloro-1H-indole-2-carboxylic acidHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 131725782trans 3-Amino-4-carbomethoxymethyl-3,4-dihydrocarbostyril trifluoroacetic acid salt

Produkt 1

HCID 69196909(3R*,4S*)-4-carbomethoxymethyl-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyrilAusbeute 56 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A 1 mL reaction vessel was charged with trans 3-amino-4-carbomethoxymethyl-3,4-dihydrocarbostyril trifluoroacetic acid salt (13 mg, 0.04 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (9 mg, 0.05 mmol), 1-hydroxy-7-azabenzotriazole (7 mg, 0.05 mmol), 5-chloroindole-2-carboxylic acid (8 mg, 0.04 mmol) and N,N-dimethylformamide (0.3 mL). After the solids dissolved during stirring at room temperature under argon, diisopropylethylamine (14 mg, 0.11 mmol) was added, and the solution was stirred for 1 h before it was diluted with water (0.2 mL) and methanol (0.8 mL). Purification by reverse phase preparative HPLC using trifluoroacetic acid containing solvents gave the title compound (8.5 mg, 56% yield) as a white solid. 1H NMR (d8-THF, 400 MHz) δ 11.2 (s, 1H), 9.6 (s, 1H), 8.06 (d, 1H, J=8.9 Hz), 7.64 (d, 1H, J=1.9 Hz), 7.43 (d, 1H, J=8.7 Hz), 7.24–6.87 (m, 6H), 4.84 (dd, 1H, J=8.8, 13.0 Hz), 3.67 (m, 1H), 3.59 (s, 3H), 2.89 (d, 2H, J=6.2 Hz). HPLC/MS [M+H]+, 412.

Aufarbeitung

  1. customA 1 mL reaction vessel
  2. dissolutionAfter the solids dissolved
  3. stirringthe solution was stirred for 1 h before it
  4. customPurification by reverse phase preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-61481d47f7f540eabd244280fdc4ba8c
Quelldatensatz
uspto-grants-2006_08
Patentnummer
US07098235B2

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