Hydrochloric Acid → 2-(1-(1-Methylethyl)-1H-pyrazol-5-yl)-3-pyridinemethanol

HRID 1471710Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1471710
COC1C=C(C([O:11][CH2:12][C:13]2[C:14]([C:19]3[N:23](C)[N:22]=[CH:21][CH:20]=3)=[N:15][CH:16]=[CH:17][CH:18]=2)=CN=1)C=O.Cl.[CH:26]([NH:29][NH2:30])([CH3:28])[CH3:27].Cl.[CH3:32][CH2:33][OH:34]>>[CH:26]([N:29]1[C:19]([C:14]2[C:13]([CH2:12][OH:11])=[CH:18][CH:17]=[CH:16][N:15]=2)=[CH:20][CH:21]=[N:30]1)([CH3:28])[CH3:27].[CH:26]([N:22]1[CH:21]=[CH:20][C:19]([C:14]2[CH:13]=[CH:18][C:32]([CH2:33][OH:34])=[CH:16][N:15]=2)=[N:23]1)([CH3:28])[CH3:27]

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 855731-Isopropylhydrazine hydrochlorideHCID 716221842-methoxy-5-((2-(1-methyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)isonicotinaldehyde

Produkt 2

HCID 89654686(2-(1-isopropyl-1H-pyrazol-3-yl)pyridin-5-yl)methanolAusbeute 25 %HCID 896547582-(1-(1-Methylethyl)-1H-pyrazol-5-yl)-3-pyridinemethanolAusbeute 71 %

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To (E)-1-(3-((tert-butyldimethylsilyloxy)methyl)pyridin-2-yl)-3-(dimethylamino)prop-2-en-1-one (crude, 1.03 g, 3.22 mmol, 1 eq.; refer to Example 46) in EtOH (10 mL) was added isopropylhydrazine hydrochloride (430 mg, 3.86 mmol, 1.2 eq.). The mixture was heated at 80° C. for 2 h, cooled, added HCl (6 N, 0.5 mL), and stirred O/N. The mixture was concentrated and diluted with EtOAc (80 mL) and NaHCO3(sat) (10 mL) solution. The layers were separated and the aqueous layer was extracted with EtOAc three times. The combined organic layers were dried over Na2SO4, concentrated, and purified on silica gel using EtOAc as eluent to give (2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methanol (500 mg, 71%) and (2-(1-isopropyl-1H-pyrazol-3-yl)pyridin-5-yl)methanol (55 mg, 25%) as pale yellow oils. Data for 2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methanol: 1H NMR (400 MHz, CDCl3) δ 8.67 (dd, J=4.7, 1.5 Hz, 1H), 8.0 (d, J=7.8 Hz, 1H), 7.61 (d, J=1.8 Hz, 1H), 7.39 (dd, J=7.8, 4.8 Hz, 1H), 6.37 (d, J=1.8 Hz, 1H), 4.67 (s, 2H), 4.55 (sep, J=6.6 Hz 1H), 1.98-2.05 (br, 1H), 1.47 (d, J=6.6 Hz, 6H). LRMS (M+H+) m/z 218.1 Data for (2-(1-isopropyl-1H-pyrazol-3-yl)pyridin-5-yl)methanol: 1H NMR (400 MHz, CDCl3) δ 8.62 (dd, J=4.8, 1.6 Hz, 1H), 7.72 (d, J=7.6 Hz, 1H), 7.55 (d, J=2.4 Hz, 1H), 7.23 (dd, J=7.6, 4.8 Hz, 1H), 6.99 (dd, J=8.0, 6.5 Hz, 1H), 6.07 (t, J=7.6 Hz, 1H), 4.67 (d, J=7.6 Hz, 2H), 4.58 (sep, J=6.7 Hz, 1H), 1.60 (d, J=6.7 Hz, 1H). LRMS (M+H+) m/z 218.1

Aufarbeitung

  1. temperaturecooled
  2. concentrationThe mixture was concentrated
  3. additiondiluted with EtOAc (80 mL) and NaHCO3(sat) (10 mL) solution
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc three times
  6. dry with materialThe combined organic layers were dried over Na2SO4
  7. concentrationconcentrated
  8. custompurified on silica gel

Quellen und Nachweise

ORD-Eintrag
ord-2fc5aa13d9eb43f19a326075ffff6c50
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09012450B2

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