Water → 3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]oxazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-6-carbonitrile

HRID 1848132Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1848132
Br[C:2]1[CH:3]=[C:4]2[N:10]=[CH:9][N:8]([CH2:11][C:12]3[CH:28]=[CH:27][C:15]4[N:16]=[C:17]([NH:19][C@@H:20]5[CH2:25][CH2:24][CH2:23][CH2:22][C@H:21]5[OH:26])[O:18][C:14]=4[CH:13]=3)[C:5]2=[N:6][CH:7]=1.O.[CH3:30][N:31](C=O)C>[C-]#N.[C-]#N.[Zn+2].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].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.[Fe+2]>[OH:26][C@@H:21]1[CH2:22][CH2:23][CH2:24][CH2:25][C@H:20]1[NH:19][C:17]1[O:18][C:14]2[CH:13]=[C:12]([CH2:11][N:8]3[C:5]4=[N:6][CH:7]=[C:2]([C:30]#[N:31])[CH:3]=[C:4]4[N:10]=[CH:9]3)[CH:28]=[CH:27][C:15]=2[N:16]=1

Komponenten

7

Edukt 3

HCID 962WaterHCID 6228DimethylformamideHCID 71549859(1R,2R)-2-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol

Produkt 1

HCID 866811013-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]oxazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-6-carbonitrileAusbeute 25,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)KatalysatorHCID 9811564Bis(dibenzylideneacetone)palladiumKatalysator

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A mixture of (1R,2R)-2-((6-((6-bromo-3H-imidazo[4,5-b]pyridin-3-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol (276 mg, 0.62 mmol), Zn(CN)2 (110 mg, 0.94 mmol), Pd2(dba)3 (57 mg, 0.062 mmol) and dppf (68.8 mg, 0.124 mmol) in DMF (6 mL) was stirred at 100° C. for 2 h. The reaction mixture was cooled to rt, poured into water (100 mL) and extracted with ethyl acetate (100 mL×2). The combined organic layers were washed with water and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 15:1 DCM/MeOH to give 3-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]oxazol-6-yl)methyl)-3H-imidazo[4,5-b]pyridine-6-carbonitrile as a light yellow solid (62 mg, 25.8%). 1H NMR (300 MHz, DMSO-d6) δ 8.85 (s, 1H), 8.83 (d, J=1.5 Hz, 1H), 8.70 (s, 1H), 7.81 (d, J=7.8 Hz, 1H), 7.41 (s, 1H), 7.14 (m, 2H), 5.54 (s, 2H), 4.68 (d, J=4.8 Hz, 1H), 3.34 (br s, 2H), 1.91 (br s, 2H), 1.62 (br s, 2H), 1.22 (br, 4H). LCMS (ESI) m/z 389 (M+H)+.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to rt
  2. extractionextracted with ethyl acetate (100 mL×2)
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel chromatography
  8. washeluting with 15:1 DCM/MeOH

Quellen und Nachweise

ORD-Eintrag
ord-9934456ad094415797e1b0914f0457f6
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08952058B2

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