HCID 59511221, Verbindung → ethyl 3-(4-methoxy-3-(2-oxo-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxylate

HRID 1157753Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1157753
Cl[C:2]1[N:3]=[CH:4][C:5]([O:32][CH3:33])=[C:6]2[C:10]([C:11](=[O:31])[C:12]([N:14]3[CH2:19][CH2:18][N:17]([C:20]4[N:24]([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[N:23]=[N:22][N:21]=4)[CH2:16][CH2:15]3)=[O:13])=[CH:9][NH:8][C:7]=12.C([Sn](CCCC)(CCCC)[C:39]1[CH:43]=[C:42]([C:44]([O:46][CH2:47][CH3:48])=[O:45])[NH:41][N:40]=1)CCC>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:33][O:32][C:5]1[CH:4]=[N:3][C:2]([C:39]2[CH:43]=[C:42]([C:44]([O:46][CH2:47][CH3:48])=[O:45])[NH:41][N:40]=2)=[C:7]2[NH:8][CH:9]=[C:10]([C:11](=[O:31])[C:12](=[O:13])[N:14]3[CH2:19][CH2:18][N:17]([C:20]4[N:24]([C:25]5[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=5)[N:23]=[N:22][N:21]=4)[CH2:16][CH2:15]3)[C:6]=12

Komponenten

5

Edukt 2

HCID 59511221HCID 59511221, VerbindungHCID 178448219HCID 178448219, Verbindung

Produkt 1

HCID 24875208ethyl 3-(4-methoxy-3-(2-oxo-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a suspension of 1-(7-chloro-4-methoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione (2.50 g, 5.35 mmol) in 1,4-dioxane (60 mL) in a sealable flask was added ethyl 3-(tributylstannyl)-1H-pyrazole-5-carboxylate (2.30 g, 5.36 mmol) followed by tetrakis(triphenylphosphine)palladium(0) (1.86 g, 1.61 mmol). The mixture was flushed with N2, the flask was sealed, and the mixture was heated to 120° C. for 16 hr. The mixture was cooled to rt and diluted with MeOH (50 mL). The remaining solids were removed by filtering the mixture through a pad of celite and were washed with MeOH (25 mL). The remaining solvent was concentrated under reduced pressure. The resulting residue was dissolved in MeOH, and loaded onto a silica gel. After the silica was dry, a column was run using the biotage system with a 0 to 10% MeOH in CH2Cl2 gradient. After concentrating the desired fractions, 1.05 g of ethyl 3-(4-methoxy-3-(2-oxo-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxylate was recovered as an orange solid. LCMS: m/e 571.2 (M+H)+, ret time 2.01 min (method 2). 1H NMR (500 MHz, DMSO-D6) δ ppm 12.39-12.72 (m, 1H) 8.37 (s, 1H) 8.11 (s, 1H) 7.52-7.76 (m, 6H) 4.68-4.85 (m, 1H) 4.38 (q, J=7.02 Hz, 2H) 3.98-4.06 (m, 3H) 3.67-3.73 (m, 2H) 3.43-3.49 (m, 2H) 3.28-3.36 (m, 2H) 3.14-3.22 (m, 2H) 1.36 (t, J=7.17 Hz, 3H).

Aufarbeitung

  1. customThe mixture was flushed with N2
  2. customthe flask was sealed
  3. temperatureThe mixture was cooled to rt
  4. additiondiluted with MeOH (50 mL)
  5. customThe remaining solids were removed
  6. filtrationby filtering the mixture through a pad of celite
  7. washwere washed with MeOH (25 mL)
  8. concentrationThe remaining solvent was concentrated under reduced pressure
  9. dissolutionThe resulting residue was dissolved in MeOH
  10. customAfter the silica was dry
  11. concentrationAfter concentrating the desired fractions, 1.05 g of ethyl 3-(4-methoxy-3-(2-oxo-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)acetyl)-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxylate
  12. customwas recovered as an orange solid
  13. customm/e 571.2 (M+H)+, ret time 2.01 min (method 2)

Quellen und Nachweise

ORD-Eintrag
ord-4c0b70dec2be46be95dcdc147c0b0c7b
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07807676B2

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