Methyl malonyl chloride → 3-[2-(4-Benzyloxyphenyl)-1-cyclohexyl-1H-benzimidazole-5-sulfonylamino]-3-oxo-propionic acid methyl ester

HRID 392992

Reaktionsgleichung

Reaktionsgleichung von HRID 392992
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:19]([CH:20]3[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]3)[C:18]3[CH:26]=[CH:27][C:28]([S:30]([NH2:33])(=[O:32])=[O:31])=[CH:29][C:17]=3[N:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:44][O:45][C:46](=[O:51])[CH2:47][C:48](Cl)=[O:49]>ClCCl>[CH3:44][O:45][C:46](=[O:51])[CH2:47][C:48]([NH:33][S:30]([C:28]1[CH:27]=[CH:26][C:18]2[N:19]([CH:20]3[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]3)[C:15]([C:12]3[CH:11]=[CH:10][C:9]([O:8][CH2:1][C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)=[CH:14][CH:13]=3)=[N:16][C:17]=2[CH:29]=1)(=[O:32])=[O:31])=[O:49]

Komponenten

5

Edukt 3

HCID 123460Methyl malonyl chlorideHCID 2733832Lithium HexamethyldisilazideHCID 226608052-[4-(Benzyloxy)phenyl]-1-cyclohexyl-1H-benzimidazole-5-sulfonamide

Produkt 1

HCID 698964073-[2-(4-Benzyloxyphenyl)-1-cyclohexyl-1H-benzimidazole-5-sulfonylamino]-3-oxo-propionic acid methyl esterAusbeute 7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of intermediate 69 (0.046 g, 0.1 mmol) in dichloromethane (0.700 mL) was cooled to 0° C. Lithium bis(trimethylsilyl)amide (1.0 M solution in tetrahydrofuran) (0.10 ml, 0.10 mmol) was added and the mixture was stirred for 1 hr. Methyl-3-chloro-3-oxo-propionate (0.011 ml, 0.10 mmol was added. The reaction mixture was stirred at rt overnight. The reaction mixture was concentrated and the residue purified by reverse phase HPLC (C18 column, water/acetonitrile gradient containing 0.05% trifluoroacetic acid) to afford the product (0.005 g, 7%). 1H NMR (CDCl3) δ 8.60 (s, 1H), 8.16 (d, 1H, J=8.8 Hz), 7.85 (d, 1H, J=8.8 Hz), 7.64 (d, 2H, J=8.8 Hz), 7.50-7.38 (m, 5H), 7.21 (d, 2H, J=8.8 Hz), 5.18 (s, 2H), 4.49 (m, 1H), 3.70 (s, 3H), 3.35 (s, 2H), 2.30 (br m, 2H), 2.02 (br m, 4H), 1.82 (br m, 1H), 1.35 (br m, 3H); ESI-MS m/e 562.18(M+1); HPLC purity (UV) 99%.

Aufarbeitung

  1. stirringThe reaction mixture was stirred at rt overnight
  2. concentrationThe reaction mixture was concentrated
  3. customthe residue purified by reverse phase HPLC (C18 column, water/acetonitrile gradient containing 0.05% trifluoroacetic acid)

Quellen und Nachweise

ORD-Eintrag
ord-3152a617be2543aa8943526729575420
Quelldatensatz
uspto-grants-2004_10
Patentnummer
US06803374B2

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