Cyclohexanemethylamine → (RS)-2-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(3,5-difluoro-phenyl)-N-cyclohexylmethylacetamide

HRID 18066

Reaktionsgleichung

Reaktionsgleichung von HRID 18066
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:32]2[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=2)[N:9]2[CH2:12][CH:11]([C:13](C)([C:23]3[CH:28]=[C:27]([F:29])[CH:26]=[C:25]([F:30])[CH:24]=3)[C:14]([NH:16]C3CCCCC3)=[O:15])[CH2:10]2)=[CH:4][CH:3]=1.N[CH2:40][CH:41]1[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]1.Cl.CN(C)CCCN=C=NCC.O.OC1C2N=NNC=2C=CC=1.Cl.ClC1C=CC(C(C2C=CC(Cl)=CC=2)N2CC(C(C3C=C(F)C=C(F)C=3)C(O)=O)C2)=CC=1>ClCCl.C(N(CC)CC)C>[Cl:38][C:35]1[CH:34]=[CH:33][C:32]([CH:8]([C:5]2[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=2)[N:9]2[CH2:12][CH:11]([CH:13]([C:23]3[CH:24]=[C:25]([F:30])[CH:26]=[C:27]([F:29])[CH:28]=3)[C:14]([NH:16][CH2:40][CH:41]3[CH2:46][CH2:45][CH2:44][CH2:43][CH2:42]3)=[O:15])[CH2:10]2)=[CH:37][CH:36]=1

Komponenten

8

Edukt 5

HCID 76688CyclohexanemethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 68584946{1-[Bis(4-chlorophenyl)methyl]-azetidin-3-yl}-(3,5-difluorophenyl)acetic acid hydrochlorideHCID 68588081(RS)-2-{1-[Bis(4-chlorophenyl)methyl]-azetidin-3-yl}-2-(3,5-difluorophenyl)-N-cyclohexyl-methylacetamideHCID 178526939HCID 178526939, Verbindung

Produkt 1

HCID 22506645(RS)-2-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(3,5-difluoro-phenyl)-N-cyclohexylmethylacetamide

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 8471TriethylamineLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

(RS)-2-{1-[Bis(4-chlorophenyl)methyl]-azetidin-3-yl}-2-(3,5-difluorophenyl)-N-cyclohexyl-methylacetamide may be prepared in the following manner: 0.016 cm3 of aminomethylcyclohexane, 29 mg of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 0.028 cm3 of triethylamine and 1.5 mg of hydroxybenzotriazole hydrate are successively added to a solution of 50 mg of {1-[bis(4-chlorophenyl)methyl]-azetidin-3-yl}-(3,5-difluorophenyl)acetic acid hydrochloride in 2 cm3 of anhydrous dichloromethane, at a temperature in the region of 20° C. The solution obtained is stirred at a temperature in the region of 20° C. for about 12 hours. The reaction medium is deposited on a Varian cartridge (6 cm3) filled with 3 g of fine silica (0.040-0.063 mm), conditioned and then eluted with dichloromethane with the aid of a Duramat pump, collecting 2-cm3 fractions. Fractions 2 to 3 are combined and concentrated to dryness under reduced pressure (2.7 kPa) at 40° C. 49 mg of (RS)-2-{1-[bis(4-chlorophenyl)methyl]azetidin-3-yl}-2-(3,5-difluoro-phenyl)-N-cyclohexylmethylacetamide are thus obtained in the form of a white foam [1H NMR spectrum (300 MHz, CDCl3, δ in ppm): from 0.75 to 1.75 (mt: 11H); 2.65 (mt: 1H); from 2.85 to 3.15 (mt: 5H); 3.42 (broad t, J=7.5 Hz: 1H); 3.57 (d, J=10.5 Hz: 1H); 4.27 (s: 1H); 5.40 (mt: 1H); 6.71 (broad t, J=9 Hz: 1H); 6.83 (mt: 2H); from 7.15 to 7.40 (mt: 8H)].

Aufarbeitung

  1. customThe solution obtained
  2. additionfilled with 3 g of fine silica (0.040-0.063 mm)
  3. washeluted with dichloromethane with the aid of a Duramat pump
  4. customcollecting 2-cm3 fractions
  5. concentrationconcentrated to dryness under reduced pressure (2.7 kPa) at 40° C

Quellen und Nachweise

ORD-Eintrag
ord-b42979186d704a598a25838fd8780b2a
Quelldatensatz
uspto-grants-2010_06
Patentnummer
US07741316B2

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