Binap, (A+-)- → 4-((3-ethyl-1-methyl-1H-pyrazol-5-yl)methylamino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one

HRID 530826Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 530826
Br[C:2]1[C:3](=[O:22])[N:4]([CH3:21])[N:5]=[C:6]([O:8][CH2:9][C@H:10]2[CH2:12][C@@H:11]2[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][N:14]=2)[CH:7]=1.[CH2:23]([C:25]1[CH:29]=[C:28]([CH2:30][NH2:31])[N:27]([CH3:32])[N:26]=1)[CH3:24].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH2:23]([C:25]1[CH:29]=[C:28]([CH2:30][NH:31][C:2]2[C:3](=[O:22])[N:4]([CH3:21])[N:5]=[C:6]([O:8][CH2:9][C@H:10]3[CH2:12][C@@H:11]3[C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][N:14]=3)[CH:7]=2)[N:27]([CH3:32])[N:26]=1)[CH3:24]

Komponenten

8

Edukt 4

HCID 634876Binap, (A+-)-HCID 23006075(3-Ethyl-1-methyl-1H-pyrazol-5-yl)methanamineHCID 23676156Sodium t-butoxideHCID 904192134-bromo-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl) methoxy)-2-methylpyridazin-3(2H)-one

Produkt 1

HCID 904544054-((3-ethyl-1-methyl-1H-pyrazol-5-yl)methylamino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

To a solution of 4-bromo-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one (70 mg, 0.19 mmol) in toluene (5 mL) under N2, ((3-ethyl-1-methyl-1H-pyrazol-5-yl)methanamine (32.2 mg, 0.23 mmol), Pd2(dba)3 (18 mg, 0.019 mmol), BINAP (35 mg, 0.06 mmol) and NaOtBu (27 mg, 0.285 mmol) were added. After the reaction mixture was stirred at 100° C. overnight, 15 mL water was added. The mixture was extracted with EtOAc (2×10 mL). The combined organics were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by Prep-HPLC to give the title compound as oil. 1H NMR (400 MHz, CDCl3) δ 8.43 (s, 1H), 7.73 (d, 1H), 7.21 (d, 1H), 6.14 (s, 1H), 5.75 (s, 1H), 4.45-4.28 (m, 3H), 4.00 (d, 4H), 3.89 (s, 3H), 3.67 (s, 3H), 2.66 (d, 2H), 2.53 (s, 1H), 1.88 (s, 1H), 1.41 (s, 2H), 1.22 (t, 3H).

Aufarbeitung

  1. extractionThe mixture was extracted with EtOAc (2×10 mL)
  2. dry with materialThe combined organics were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by Prep-HPLC

Quellen und Nachweise

ORD-Eintrag
ord-cc22ce6dda9f43ebbf0b3ece51937e9d
Quelldatensatz
uspto-grants-2016_05
Patentnummer
US09353104B2

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