Potassium Carbonate → 5-{2-[4-(4-Methyl-benzothiazol-2-yloxy)-phenyl]-ethyl}-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid amide

HRID 384532Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 384532
Cl.[CH2:2]1[CH:6]2[CH2:7][NH:8][CH2:9][CH:5]2[CH2:4][N:3]1[C:10]([NH2:12])=[O:11].[CH2:13]1C2CNCC2CN1C(N)=O.C([O-])([O-])=O.[K+].[K+].CS([CH2:34][CH2:35][C:36]1[CH:52]=[CH:51][C:39]([O:40][C:41]2[S:42][C:43]3[CH:49]=[C:48](C)[CH:47]=[CH:46][C:44]=3[N:45]=2)=[CH:38][CH:37]=1)(=O)=O>C(Cl)Cl.CO.C(O)(CC)(C)C>[CH3:13][C:46]1[C:44]2[N:45]=[C:41]([O:40][C:39]3[CH:38]=[CH:37][C:36]([CH2:35][CH2:34][N:8]4[CH2:7][CH:6]5[CH2:2][N:3]([C:10]([NH2:12])=[O:11])[CH2:4][CH:5]5[CH2:9]4)=[CH:52][CH:51]=3)[S:42][C:43]=2[CH:49]=[CH:48][CH:47]=1

Komponenten

7

Edukt 4

HCID 11430Potassium CarbonateHCID 57448388Hexahydropyrrolo[3,4-c]pyrrole-2(1h)-carboxamide hydrochlorideHCID 57448389Hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid amideHCID 67206214HCID 67206214, Verbindung

Produkt 1

HCID 425976575-{2-[4-(4-Methyl-benzothiazol-2-yloxy)-phenyl]-ethyl}-hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid amideAusbeute 5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 64052-Methyl-2-butanolLösungsmittelHCID 21226129Dichloromethane methanolLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A solution of hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid amide hydrochloride in 50% CH2Cl2/CH3OH was treated with DOWEX Monosphere 550A (OH) anion-exchange resin to afford the free base. The DOWEX resin was filtered and the resulting solution was concentrated and used without further purification. To a solution of this hexahydro-pyrrolo[3,4-c]pyrrole-2-carboxylic acid amide (85 mg, 0.54 mmol) and K2CO3 (116 mg, 0.84 mmol) in tert-amyl alcohol (2.6 mL) was added 2-[4-(2-methanesulfonyl-ethyl)-phenoxy]-6-methyl-benzothiazole (120 mg, 0.34 mmol). The reaction mixture was heated to 80° C. for 16 h. The reaction mixture was filtered and washed with CH3OH. The resulting liquid was purified by preparative reverse phase HPLC to afford the title compound (11 mg, 5%). MS (ESI): mass calcd. for C23H26N4O2S, 422.55; m/z found, 423.2 [M+H]+. 1H NMR (500 MHz, CDCl3): 7.62 (d, J=8.3 Hz, 1H), 7.48 (s, 1H), 7.28 (s, 4H), 7.20 (dd, J=8.3, 1.1 Hz, 1H), 4.39 (s, 2H), 3.60 (dd, J=10.2, 8.2 Hz, 2H), 3.30 (dd, J=10.0, 1.9 Hz, 2H), 2.98-2.87 (m, 2H), 2.86-2.80 (m, 2H), 2.76 (dd, J=9.3, 6.9 Hz, 2H), 2.74-2.67 (m, 2H), 2.53 (dd, J=9.3, 3.4 Hz, 2H), 2.45 (s, 3H).

Aufarbeitung

  1. customto afford the free base
  2. filtrationThe DOWEX resin was filtered
  3. concentrationthe resulting solution was concentrated
  4. customused without further purification
  5. filtrationThe reaction mixture was filtered
  6. washwashed with CH3OH
  7. customThe resulting liquid was purified by preparative reverse phase HPLC

Quellen und Nachweise

ORD-Eintrag
ord-6bf6d45f4fd548579908aa21b9b3b883
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08367719B2

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