Triethylamine → N-((1R,2S)-2-{[(3aR,4R,9bR)-4-(Methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexyl)-N'-[4-(1H-pyrazol-1-yl)phenyl]urea

HRID 550308

Reaktionsgleichung

Reaktionsgleichung von HRID 550308
[N:1]1([C:6]2[CH:14]=[CH:13][C:9](C(O)=O)=[CH:8][CH:7]=2)[CH:5]=[CH:4][CH:3]=[N:2]1.C([N:17]([CH2:20]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:29])C=CC=CC=1.Cl.Cl.[CH3:41][O:42][CH2:43][C@H:44]1[C@H:53]2[CH2:54][CH2:55][N:56]([C:57]([C@H:59]3[CH2:64][CH2:63][CH2:62][CH2:61][C@H:60]3[NH2:65])=[O:58])[C@H:52]2[C:51]2[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=2[NH:45]1>C1(C)C=CC=CC=1.O1CCCC1.O>[CH3:41][O:42][CH2:43][C@H:44]1[C@H:53]2[CH2:54][CH2:55][N:56]([C:57]([C@H:59]3[CH2:64][CH2:63][CH2:62][CH2:61][C@H:60]3[NH:65][C:20]([NH:17][C:9]3[CH:8]=[CH:7][C:6]([N:1]4[CH:5]=[CH:4][CH:3]=[N:2]4)=[CH:14][CH:13]=3)=[O:29])=[O:58])[C@H:52]2[C:51]2[CH:50]=[CH:49][CH:48]=[CH:47][C:46]=2[NH:45]1

Komponenten

8

Edukt 4

HCID 8471Triethylamine2×HCID 199401P,P-Diphenylphosphinic azideHCID 7365274-(1H-pyrazol-1-yl)benzoic acidHCID 67150533(1R,2S)-2-{[(3aR,4R,9bR)-4-(methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexaneamine dihydrochloride

Produkt 1

HCID 57847222N-((1R,2S)-2-{[(3aR,4R,9bR)-4-(Methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexyl)-N'-[4-(1H-pyrazol-1-yl)phenyl]ureaAusbeute 76,5 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a suspension of 4-(1H-pyrazol-1-yl)benzoic acid (271 mg, 1.44 mmol) in toluene (5 ml) were added triethylamine (0.200 ml, 1.44 mmol) and diphenylphosphorylazide (0.310 ml, 1.44 mmol) at room temperature, and the mixture was stirred at 80° C. for 2 hrs. This reaction mixture was allowed to cool to room temperature and added dropwise to a solution of (1R,2S)-2-{[(3aR,4R,9bR)-4-(methoxymethyl)-2,3,3a,4,5,9b-hexahydro-1H-pyrrolo[3,2-c]quinolin-1-yl]carbonyl}cyclohexaneamine dihydrochloride (200 mg, 0.480 mmol) and triethylamine (0.200 ml, 1.44 mmol) in tetrahydrofuran (5 ml). The mixture was stirred at room temperature for 3 hrs., water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogen carbonate solution, dried over anhydrous MgSO4, and concentrated under reduced pressure. The obtained residue was subjected to column chromatography using silica gel and eluted with hexane-ethyl acetate (5:5-0:1) to give the title compound (194 mg, 76%) as an amorphous form.

Aufarbeitung

  1. temperatureto cool to room temperature
  2. stirringThe mixture was stirred at room temperature for 3 hrs
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with aqueous sodium hydrogen carbonate solution
  5. dry with materialdried over anhydrous MgSO4
  6. concentrationconcentrated under reduced pressure
  7. washeluted with hexane-ethyl acetate (5:5-0:1)

Quellen und Nachweise

ORD-Eintrag
ord-ab2d7521990c4acb96b24af3cee7d752
Quelldatensatz
uspto-grants-2011_05
Patentnummer
US07943770B2

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