Methanol → 4-({[({[4-(3,4-Dichlorobenzyl)-1,4-oxazepan-2-yl]methyl}amino)carbonyl]amino}methyl)benzamide

HRID 1371457Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1371457
[C:1]([N:8]1[CH:12]=[CH:11]N=C1)([N:3]1[CH:7]=[CH:6]N=C1)=[O:2].[Cl:13][C:14]1[CH:15]=[C:16]([CH:27]=[CH:28][C:29]=1[Cl:30])[CH2:17][N:18]1[CH2:24][CH2:23][CH2:22][O:21]C(CN)[CH2:19]1.NCC1[CH:41]=[CH:40][C:36]([C:37]([NH2:39])=[O:38])=[CH:35][CH:34]=1.CO>ClCCl>[Cl:13][C:14]1[CH:15]=[C:16]([CH:27]=[CH:28][C:29]=1[Cl:30])[CH2:17][N:18]1[CH2:24][CH2:23][CH2:22][O:21][CH:11]([CH2:12][NH:8][C:1]([NH:3][CH2:7][C:6]2[CH:41]=[CH:40][C:36]([C:37]([NH2:39])=[O:38])=[CH:35][CH:34]=2)=[O:2])[CH2:19]1

Komponenten

6

Edukt 4

HCID 887MethanolHCID 682631,1'-CarbonyldiimidazoleHCID 25128184-(Aminomethyl)benzamideHCID 17984703[4-(3,4-Dichlorobenzyl)-1,4-oxazepan-2-yl]methylamine

Produkt 1

HCID 179847174-({[({[4-(3,4-Dichlorobenzyl)-1,4-oxazepan-2-yl]methyl}amino)carbonyl]amino}methyl)benzamideAusbeute 15,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel3×

Reaktionsbedingungen

Temperatur
22 °C

Versuchsvorschrift

To a solution of 1,1′-carbonyldiimidazole (0.041 g) in dichloromethane (2 ml) at 0° C. was added dropwise a solution of Intermediate 41 (0.079 g) in dichloromethane (2 ml). The mixture was stirred at 0° C. for 1 h and at 22° C. for 1 h, re-cooled to approximately 0° C. and a solution of 4-aminomethylbenzamide (0.041 g) in a 1:1 mixture of dichloromethane and N,N-dimethylformiamide (4 ml) was added dropwise. The mixture was stirred at 0° C. for 1 h and at 22° C. for 1 h, and applied in two equal portions to ion exchange cartridges (2 g Isolute SCX pre-conditioned with methanol). Elution with methanol (3 column volumes) followed 10% 0.880 ammonia in methanol (2 column volumes) and evaporation of the basic fractions in vacuo gave the crude product. Purification by Biotage flash chromatography on a silica gel cartridge (89), eluting with 150:8:1 dichloromethane/ethanol/0.880 ammonia, gave the title compound as a white solid (0.0186 g).

Aufarbeitung

  1. temperaturere-cooled to approximately 0° C.
  2. additionwas added dropwise
  3. stirringThe mixture was stirred at 0° C. for 1 h and at 22° C. for 1 h
  4. washElution with methanol (3 column volumes)
  5. custom10% 0.880 ammonia in methanol (2 column volumes) and evaporation of the basic fractions in vacuo
  6. customgave the crude product
  7. customPurification by Biotage flash chromatography on a silica gel cartridge (89)
  8. washeluting with 150:8:1 dichloromethane/ethanol/0.880 ammonia

Quellen und Nachweise

ORD-Eintrag
ord-4497836d24894878a41f9144eb1605bc
Quelldatensatz
uspto-grants-2007_01
Patentnummer
US07157457B2

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