2-Chlorobenzoic Acid → HCID 19783221, Verbindung

HRID 257557Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 257557
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:23]([C:27]1[C:31]([CH2:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[S:45](=[O:48])(=[O:47])[NH2:46])=[CH:35][CH:34]=2)=[C:30]([C:49]([O:51][CH2:52][CH3:53])=[O:50])[N:29]([C:54]2[CH:59]=[C:58]([N+:60]([O-:62])=[O:61])[CH:57]=[CH:56][C:55]=2[Cl:63])[N:28]=1)[CH2:24][CH2:25][CH3:26].N12CCCN=C1CCCCC2>C1COCC1>[CH2:23]([C:27]1[C:31]([CH2:32][C:33]2[CH:38]=[CH:37][C:36]([C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=3[S:45](=[O:48])(=[O:47])[NH:46][C:4](=[O:6])[C:3]3[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=3[Cl:1])=[CH:35][CH:34]=2)=[C:30]([C:49]([O:51][CH2:52][CH3:53])=[O:50])[N:29]([C:54]2[CH:59]=[C:58]([N+:60]([O-:62])=[O:61])[CH:57]=[CH:56][C:55]=2[Cl:63])[N:28]=1)[CH2:24][CH2:25][CH3:26]

Komponenten

6

Edukt 4

HCID 83742-Chlorobenzoic AcidHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 19783238HCID 19783238, Verbindung

Produkt 1

HCID 19783221HCID 19783221, VerbindungAusbeute 48 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A mixture of 675 mg (4.28 mmol) of 2-chlorobenzoic acid, 695 mg (4.28 mmol) of 1,1'-carbonyldiimidazole (CDI), and 2 mL of dry THF was stirred at 50° C. under N2 for 3 hours. Then a solution of 851 mg (1.43 mmol) of ethyl 3-n-butyl-1-(2-chloro-5-nitrophenyl)-4-[(2'-sulfamoylbiphenyl-4-yl)methyl]-1H-pyrazole-5-carboxylate (from Step G) and 640 μL (651 mg, 4.28 mmol) of 1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU) in 5 mL of dry THF was added, and stirring under N2 at 50° C. was continued overnight. The cooled reaction mixture was partitioned between 75 mL of 5% citric acid (aqueous) and 75 mL of ethyl acetate. The organic phase was washed with H2O, dried (Na2SO4), filtered, and concentrated. The orange residue was flash chromatographed on silica gel (elution with 1% MeOH in CH2Cl2) to yield 503 mg (48%) of the title compound as a solid, mp>60° C. (gradual); homogeneous by TLC in 95:5 CH2Cl2 --MeOH; mass spectrum (FAB) m/e 736 (M+1)+. 400 MHz 1H NMR (CDCl3) δ0.88 (t, J=7.3 Hz, 3H), 1.05 (t, J=7.1 Hz, 3H), 1.34 (m, 2H), 1.59 (m, 2H, partially obscured by H2O peak), 2.56 (t, J=7.8 Hz, 2H), 4.14 (q, J=7.1 Hz, 2H), overlapping 4.16 (s, 2H), 7.07 (d, J=8.1 Hz, 2H), 7.25-7.45 (m, 6H), 7.55-7.69 (m, 4H), 8.26 (dd, J=8.8, 2.6 Hz, 1H), 8.35 (dd, J=8.1, 1.3 Hz, 2H).

Aufarbeitung

  1. stirringstirring under N2 at 50° C.
  2. waitwas continued overnight
  3. customThe cooled reaction mixture
  4. customwas partitioned between 75 mL of 5% citric acid (aqueous) and 75 mL of ethyl acetate
  5. washThe organic phase was washed with H2O
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customchromatographed on silica gel (elution with 1% MeOH in CH2Cl2)

Quellen und Nachweise

ORD-Eintrag
ord-eb67d4bb00af4e0db7963a96b374e9ec
Quelldatensatz
uspto-grants-1993_11
Patentnummer
US05262412

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