Sodium hydride → 4-[3-(4-Formyl-3-methyl-phenoxy)-propyl]-5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester

HRID 647000Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 647000
ClC1C=C(C)C2N=C(C3C=CC(OCCCN4C(=O)CCNCC4)=CC=3C)NC=2C=1.[C:31]([O:35][C:36]([N:38]1[CH2:44][CH2:43][C:42](=[O:45])[NH:41][CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].[H-].[Na+].I[CH2:49][CH2:50][CH2:51][O:52][C:53]1[CH:60]=[CH:59][C:56]([CH:57]=[O:58])=[C:55]([CH3:61])[CH:54]=1>CN(C=O)C.O>[C:31]([O:35][C:36]([N:38]1[CH2:44][CH2:43][C:42](=[O:45])[N:41]([CH2:49][CH2:50][CH2:51][O:52][C:53]2[CH:60]=[CH:59][C:56]([CH:57]=[O:58])=[C:55]([CH3:61])[CH:54]=2)[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]

Komponenten

7

Edukt 4

HCID 24758Sodium hydrideHCID 226177365-Oxo-(1,4)diazepane-1-carboxylic acid tert-butyl esterHCID 574347584-(3-Iodo-propoxy)-2-methyl-benzaldehydeHCID 598122164-{3-[4-(6-Chloro-4-methyl-1H-benzoimidazol-2-yl)-3-methyl-phenoxy]-propyl}-[1,4]diazepan-5-one

Produkt 1

HCID 575254384-[3-(4-Formyl-3-methyl-phenoxy)-propyl]-5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

4-{3-[4-(6-Chloro-4-methyl-1H-benzoimidazol-2-yl)-3-methyl-phenoxy]-propyl}-[1,4]diazepan-5-one. To a stirred solution of 5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester (3.0 g, 14.0 mmol, 1.0 equiv) in DMF (45 mL) at rt was added 60% sodium hydride (560 mg, 14.0 mmol, 1.0 equiv). After stirring for 30 min, 4-(3-iodo-propoxy)-2-methyl-benzaldehyde (4.26 g, 14.0 mmol, 1.0 equiv) was added as a solution in DMF (5 mL). The mixture was stirred for 16 h and then poured into water and extracted with ethyl acetate. The combined extracts were dried (Na2SO4), filtered, and concentrated. The residue was partially purified by column chromatography (silica gel, 5-50% ethyl acetate in hexanes) to afford 4-[3-(4-formyl-3-methyl-phenoxy)-propyl]-5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester as a mixture with several unidentified products. This impure mixture (200 mg), 5-chloro-3-methyl-benzene-1,2-diamine (80.1 mg), and Na2S2O5 (97 mg) were stirred in DMF (1.0 mL) at 90° C. for 3 h. After cooling to rt, the reaction mixture was loaded on silica gel and was purified by Method 2 to afford 4-{3-[4-(6-chloro-4-methyl-1H-benzoimidazol-2-yl)-3-methyl-phenoxy]-propyl}-5-oxo-[1,4]diazepane-1-carboxylic acid tert-butyl ester as a mixture with several unidentified products. This mixture was dissolved in dichloromethane (1.0 mL) and TFA (1.0 mL) and stirred at rt for 1 h. The reaction mixture was loaded on silica gel and purified by Method 2 to afford 91.0 mg (42%) of the title compound. MS (electrospray): mass calculated for C23H27ClN4O2, 426.18; m/z found, 427.4 [M+H]+. 1H NMR (400 MHz, CD3OD): 7.55 (d, J=8.5 Hz, 1H), 7.42 (br s, 1H), 7.09-7.06 (m, 1H), 6.97 (d, J=2.4 Hz, 1H), 6.93 (dd, J=8.5, 2.5 Hz, 1H), 4.10 (t, J=6.1 Hz, 2H), 3.67-3.56 (m, 4H), 2.98-2.89 (m, 4H), 2.72-2.66 (m, 2H), 2.59 (s, 3H), 2.50 (s, 3H), 2.12-2.01 (m, 2H).

Aufarbeitung

  1. stirringThe mixture was stirred for 16 h
  2. extractionextracted with ethyl acetate
  3. dry with materialThe combined extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was partially purified by column chromatography (silica gel, 5-50% ethyl acetate in hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-0c48ad8a21024235bfb5873a12d12aeb
Quelldatensatz
uspto-grants-2010_04
Patentnummer
US07705143B2

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