HCID 90112160, Verbindung → US11401286, Example 140

HRID 1508810Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1508810
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][C:22](OCC)=[O:23])=[CH:17][CH:16]=3)[CH:11]=[C:10]([CH:27]3[CH2:29][CH2:28]3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([CH2:21][CH2:22][OH:23])=[CH:17][CH:16]=3)[CH:11]=[C:10]([CH:27]3[CH2:29][CH2:28]3)[N:9]=2)[CH:5]=[CH:6][CH:7]=1

Komponenten

3

Edukt 1

HCID 90112160HCID 90112160, Verbindung

Produkt 1

HCID 90111703US11401286, Example 140Ausbeute 79,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A 25-mL round bottom flask was charged with ethyl 2-(4-((2-(3-chlorophenyl)-6-cyclopropylpyridin-4-yl)amino)phenyl)acetate (0.152 g, 0.37 mmol) and THF (6 mL) at rt. Borane-dimethylsulfide complex (0.106 mL, 1.12 mmol) was added and the resulting solution was stirred at 50° C. for 2.5 h until the starting material was consumed (monitored by LCMS analysis). The reaction was quenched with methanol then treated with 2N aqueous HCl (5 drops) and concentrated under reduced pressure. The residue was diluted with methanol and then concentrated under reduced pressure. The residue was treated with saturated sodium bicarbonate (0.1 mL) and then purified by column chromatography on silica using hexanes/ethyl acetate (10:0 to 0:10) as the eluent to afford 2-(4-((2-(3-chlorophenyl)-6-cyclopropylpyridin-4-yl)amino)phenyl)ethanol (0.107 g, 78%) as a colorless oil. MW=364.87. 1H NMR (CDCl3, 500 MHz) δ 7.94-7.92 (m, 1H), 7.81-7.76 (m, 1H), 7.35-7.30 (m, 2H), 7.27-7.23 (m, 2H), 7.18-7.14 (m, 2H), 6.99 (d, J=2.0 Hz, 1H), 6.65 (d, J=2.0 Hz, 1H), 5.94 (s, 1H), 3.90 (q, J=6.0 Hz, 2H), 2.88 (t, J=1.5 Hz, 2H), 1.99-1.92 (m, 1H), 1.40 (t, J=2.0 Hz, 1H), 1.12-1.07 (m, 2H), 0.96-0.90 (m, 2H); ESI MS m/z 365 [M+H]+. Treatment with 1.25M HCl in methanol (0.70 mL, 0.88 mmol) afforded the title compound (0.105 g, 90%) as a light yellow solid. MW=401.33. M.p. 125-128° C. 1H NMR (DMSO-d6, 500 MHz) δ 13.57 (br s, 1H), 10.50 (br s, 1H), 7.95-7.93 (m, 1H), 7.77-7.73 (m, 1H), 7.72-7.66 (m, 1H), 7.65-7.59 (m, 1H), 7.34-7.29 (m, 2H), 7.28-7.24 (m, 2H), 7.07 (s, 1H), 6.58 (br s, 1H), 3.63 (t, J=7.0 Hz, 2H), 2.74 (t, J=7.0 Hz, 2H), 2.40-2.29 (m, 1H), 1.22 (s, 2H), 1.05-0.96 (m, 2H); APCI MS m/z 365 [M+H]+.

Aufarbeitung

  1. additionBorane-dimethylsulfide complex (0.106 mL, 1.12 mmol) was added
  2. customwas consumed (monitored by LCMS analysis)
  3. customThe reaction was quenched with methanol
  4. additionthen treated with 2N aqueous HCl (5 drops)
  5. concentrationconcentrated under reduced pressure
  6. additionThe residue was diluted with methanol
  7. concentrationconcentrated under reduced pressure
  8. additionThe residue was treated with saturated sodium bicarbonate (0.1 mL)
  9. custompurified by column chromatography on silica

Quellen und Nachweise

ORD-Eintrag
ord-8694c28c21bc48e1956cd8bdde551e62
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09221843B2

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