Water → 3-(1-(4-(3-(piperidin-1-yl)propoxy)-2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(1-isopentyl-1H-pyrazol-4-yl)pyridin-2-amine

HRID 1896081Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1896081
Br[CH:2](C)[CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([N:12]2[C:16]([C:17]3[C:18]([NH2:33])=[N:19][CH:20]=[C:21]([C:23]4[CH:24]=[N:25][N:26]([CH2:28][CH2:29][CH:30]([CH3:32])[CH3:31])[CH:27]=4)[CH:22]=3)=[N:15][N:14]=[N:13]2)=[C:8]([F:34])[C:7]=1[F:35].[NH:37]1[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1.O.O1CCN(CCCCOC2C=CC(N3C(C4C(N)=NC=C(C5C=NN(CCC(C)C)C=5)C=4)=NN=N3)=C(F)C=2F)CC1>C1COCC1>[N:37]1([CH2:2][CH2:3][CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([N:12]3[C:16]([C:17]4[C:18]([NH2:33])=[N:19][CH:20]=[C:21]([C:23]5[CH:24]=[N:25][N:26]([CH2:28][CH2:29][CH:30]([CH3:32])[CH3:31])[CH:27]=5)[CH:22]=4)=[N:15][N:14]=[N:13]3)=[C:8]([F:34])[C:7]=2[F:35])[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38]1

Komponenten

6

Edukt 4

HCID 962WaterHCID 8082PiperidineHCID 67377779HCID 67377779, VerbindungHCID 673779643-(1-(4-(3-bromobutoxy)-2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(1-isopentyl-1H-pyrazol-4-yl)pyridin-2-amine2×

Produkt 1

HCID 673779123-(1-(4-(3-(piperidin-1-yl)propoxy)-2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(1-isopentyl-1H-pyrazol-4-yl)pyridin-2-amineAusbeute 78 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

As shown in step 5-iii of Scheme 5,3-(1-(4-(3-bromobutoxy)-2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(1-isopentyl-1H-pyrazol-4-yl)pyridin-2-amine (Compound 1021, 111 mg, 0.203 mmol) was dissolved in 5 mL of THF and cooled to 0° C. The mixture was treated with piperidine (0.06 mL, 0.61 mmol), warmed to 70° C., and stirred for 16 hours. The reaction was cooled to room temperature, treated with cold water, and extracted with CHCl3 (50 mL). The organics were washed with water, washed with brine, dried over sodium sulfate, filtered, and the volatiles removed under reduced pressure. The residue was purified by silica gel chromatography (5% MeOH/CHCl3) to provide 3-(1-(4-(3-(piperidin-1-yl)propoxy)-2,3-difluorophenyl)-1H-tetrazol-5-yl)-5-(1-isopentyl-1H-pyrazol-4-yl)pyridin-2-amine (Compound 150, 70 mg, 78% yield).

Aufarbeitung

  1. temperaturewarmed to 70° C.
  2. temperatureThe reaction was cooled to room temperature
  3. extractionextracted with CHCl3 (50 mL)
  4. washThe organics were washed with water
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customthe volatiles removed under reduced pressure
  9. customThe residue was purified by silica gel chromatography (5% MeOH/CHCl3)

Quellen und Nachweise

ORD-Eintrag
ord-9800c1489d6a43ddafbff17df1b4a27d
Quelldatensatz
uspto-grants-2013_08
Patentnummer
US08518938B2

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