1,1'-Carbonyldiimidazole → 5-(4-chlorophenyl)-6-cyclohexyl-N-(ethylsulfonyl)-4-(2-morpholin-4-yl-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxamide

HRID 505816Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 505816
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][C:14]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[O:15])[C:11]3[CH:22]=[C:23]([C:25]([OH:27])=O)[S:24][C:10]=3[C:9]=2[CH:28]2[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]2)=[CH:4][CH:3]=1.C1N=CN(C(N2C=NC=C2)=O)C=1.[CH2:46]([S:48]([NH2:51])(=[O:50])=[O:49])[CH3:47].C1CCN2C(=NCCC2)CC1>C1COCC1.CN(C1C=CN=CC=1)C.CCOC(C)=O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH2:13][C:14]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=[O:15])[C:11]3[CH:22]=[C:23]([C:25]([NH:51][S:48]([CH2:46][CH3:47])(=[O:50])=[O:49])=[O:27])[S:24][C:10]=3[C:9]=2[CH:28]2[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]2)=[CH:4][CH:3]=1

Komponenten

8

Edukt 4

HCID 682631,1'-CarbonyldiimidazoleHCID 73702EthanesulfonamideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 113177625-(4-Chlorophenyl)-6-cyclohexyl-4-(2-morpholin-4-yl-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylic acid

Produkt 1

HCID 112616945-(4-chlorophenyl)-6-cyclohexyl-N-(ethylsulfonyl)-4-(2-morpholin-4-yl-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxamideAusbeute 17 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 142844-(Dimethylamino)pyridineKatalysatorHCID 8028TetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

A solution (0.015 M) of 5-(4-chlorophenyl)-6-cyclohexyl-4-(2-morpholin-4-yl-2-oxoethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylic acid in THF at RT was treated with CDI (1.1 eq.) and DMAP (1.1 eq.). After stirring for 1 h at RT, ethanesulfonamide (2 eq.) and DBU (2 eq.) were added. The mixture was heated to reflux for 5 h then cooled down and diluted with AcOEt. The organic phase was washed with aqueous HCl (0.1 N) and dried. Evaporation of the solvent under reduced pressure gave a residue which was purified by RP-HPLC (Conditions: Waters X-TERRA MS C18, 10 micron, 19×100 mm; flow: 20 mL/min; Gradient: A: H2O+0.05% TFA; B: MeCN+0.05% TFA; 50% A isocratic for 1 min then linear to 20% A in 9 min) to afford the title compound (17%) as a solid.

Aufarbeitung

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 5 h
  3. temperaturethen cooled down
  4. washThe organic phase was washed with aqueous HCl (0.1 N)
  5. customdried
  6. customEvaporation of the solvent under reduced pressure
  7. customgave a residue which
  8. customwas purified by RP-HPLC (Conditions
  9. wait50% A isocratic for 1 min then linear to 20% A in 9 min

Quellen und Nachweise

ORD-Eintrag
ord-d7561cc3d4ac493eb2ea69be99beaf1b
Quelldatensatz
uspto-grants-2010_08
Patentnummer
US07781431B2

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