Triethylamine → N-(3,5-difluorobenzyl)-1-methyl-N-(2-{[(4S)-3-methyl-2,5-dioxo-1',3'-dihydrospiro-[imidazolidine-4,2'-inden]-5'-yl]amino}-2-oxoethyl)cyclohexanecarboxamide

HRID 386610

Reaktionsgleichung

Reaktionsgleichung von HRID 386610
[CH3:1][C:2]1([C:8]([OH:10])=O)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3]1.C(Cl)(=O)C(Cl)=O.C(N(CC)CC)C.[Cl-].[F:25][C:26]1[CH:27]=[C:28]([CH:51]=[C:52]([F:54])[CH:53]=1)[CH2:29][NH2+:30][CH2:31][C:32]([NH:34][C:35]1[CH:36]=[C:37]2[C:41](=[CH:42][CH:43]=1)[CH2:40][C@@:39]1([C:47](=[O:48])[NH:46][C:45](=[O:49])[N:44]1[CH3:50])[CH2:38]2)=[O:33]>C(Cl)Cl.CN(C=O)C>[F:25][C:26]1[CH:27]=[C:28]([CH:51]=[C:52]([F:54])[CH:53]=1)[CH2:29][N:30]([CH2:31][C:32]([NH:34][C:35]1[CH:36]=[C:37]2[C:41](=[CH:42][CH:43]=1)[CH2:40][C@@:39]1([C:47](=[O:48])[NH:46][C:45](=[O:49])[N:44]1[CH3:50])[CH2:38]2)=[O:33])[C:8]([C:2]1([CH3:1])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7]1)=[O:10]

Komponenten

7

Edukt 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 707441-Methylcyclohexanecarboxylic acidHCID 86647680N-(3,5-difluorobenzyl)-2-{[(4S)-3-methyl-2,5-dioxo-1',3'-dihydrospiro[imidazolidine-4,2'-inden]-5'-yl]amino}-2-oxoethanaminium chloride2×

Produkt 1

HCID 25015785N-(3,5-difluorobenzyl)-1-methyl-N-(2-{[(4S)-3-methyl-2,5-dioxo-1',3'-dihydrospiro-[imidazolidine-4,2'-inden]-5'-yl]amino}-2-oxoethyl)cyclohexanecarboxamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideKatalysatorHCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 1-methylcyclohexanecarboxylic acid (32.0 mg, 0.222 mmol) in DCM (1.5 mL) was added one drop of DMF (cat.), followed by oxalyl chloride (37.0 mg, 0.228 mmol), while at ambient temperature and under a constant stream of nitrogen. Upon cessation of gas evolution, the reaction mixture was cooled to 0° C. prior to the introduction of triethylamine (34.0 mg, 0.333 mmol) as a solution in DCM (2.0 mL), and then N-(3,5-difluorobenzyl)-2-{[(4S)-3-methyl-2,5-dioxo-1′,3′-dihydrospiro[imidazolidine-4,2′-inden]-5′-yl]amino}-2-oxoethanaminium chloride (50.0 mg, 0.111 mmol, Intermediate 1). After 1 hour the reaction mixture was applied directly to a silica gel column for purification, eluting with DCM:MeOH—99:1 to 95:5. Product containing fractions were pooled and concentrated in vacuo to give the title compound. MS: m/z=561 (M+23(Na+)). HRMS: m/z=539.2477; calculated m/z=539.2464 for C29H33N4O4F2.

Aufarbeitung

  1. customAfter 1 hour the reaction mixture was applied directly to a silica gel column for purification
  2. washeluting with DCM
  3. additionProduct containing fractions
  4. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-b6955718136e40a596cd15ee41e49d7c
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08372859B2

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