Trifluoroacetic acid → (7-Chloro-thieno[3,2-b]pyridin-2-yl)-(3-methoxy-azetidin-1-yl)-methanone

HRID 1825175Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1825175
C([N:14]1[CH2:17][CH:16]([O:18][CH3:19])[CH2:15]1)(C1C=CC=CC=1)C1C=CC=CC=1.FC(F)(F)C(O)=O.C(N(CC)CC)C.[Cl:34][C:35]1[CH:40]=[CH:39][N:38]=[C:37]2[CH:41]=[C:42]([C:44](Cl)=[O:45])[S:43][C:36]=12>C(Cl)Cl.[Pd].CCO>[Cl:34][C:35]1[CH:40]=[CH:39][N:38]=[C:37]2[CH:41]=[C:42]([C:44]([N:14]3[CH2:17][CH:16]([O:18][CH3:19])[CH2:15]3)=[O:45])[S:43][C:36]=12

Komponenten

8

Edukt 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 5975241-Benzhydryl-3-methoxyazetidineHCID 221435437-Chlorothieno[3,2-b]pyridine-2-carbonyl chloride

Produkt 1

HCID 22143554(7-Chloro-thieno[3,2-b]pyridin-2-yl)-(3-methoxy-azetidin-1-yl)-methanoneAusbeute 56 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 23938PalladiumKatalysatorHCID 702EthanolLösungsmittelHCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

A 100 ml round bottom flask was charged with 1-benzhydryl-3-methoxy-azetidine 78a (447 mg, 1.77 mmole), 10% Pd/C (300 mg), trifluoroacetic acid (0.15 ml, 1.94 mmole) and EtOH (30 ml) and placed under 1 atm H2 and vigorously stirred at rt. After 2 hr, the catalyst was removed and washed with MeOH. The filtrate was concentrated under reduced pressure to give the crude azetidine which was dissolved in CH2Cl2. To this solution were added triethylamine (0.6 ml, 4.41 mmole) and 7-chloro-thieno[3,2-b]pyridine-2-carbonyl chloride, prepared as previously described in example 25a. After stirring at ambient temperature overnight, the reaction mixture was diluted with more CH2Cl2, then washed sequentially with 0.5N HCl, satd. NaHCO3 (aq), and brine. The organic layer was dried (MgSO4) and concentrated to near dryness under reduced pressure, then triturated with hexanes to give 278 mg (56%) of the desired product as a light yellow solid. 1H NMR (DMSO-d6) δ 8.73(1H, d, J=5.1 Hz), 8.00 (1H, s), 7.70 (1H, d, J=5.1 Hz), 4.77 (1H, m), 4.49 (1H, m), 4.31 (2H, m), 3.90 (1H, m), 3.24 (3H, s). APCl m/z 283/285 (M+H)+.

Aufarbeitung

  1. customthe catalyst was removed
  2. washwashed with MeOH
  3. concentrationThe filtrate was concentrated under reduced pressure
  4. customto give the crude azetidine which
  5. customprepared
  6. stirringAfter stirring at ambient temperature overnight
  7. washwashed sequentially with 0.5N HCl
  8. dry with materialThe organic layer was dried (MgSO4)
  9. concentrationconcentrated
  10. customtriturated with hexanes

Quellen und Nachweise

ORD-Eintrag
ord-b42638b4da26478fb214998aab955285
Quelldatensatz
uspto-grants-2006_05
Patentnummer
US07045528B2

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