Water → 1-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]oxazol-6-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile

HRID 1848209Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1848209
Br[C:2]1[CH:28]=[CH:27][C:5]2[N:6]([CH2:9][C:10]3[CH:26]=[CH:25][C:13]4[N:14]=[C:15]([NH:17][C@@H:18]5[CH2:23][CH2:22][CH2:21][CH2:20][C@H:19]5[OH:24])[O:16][C:12]=4[CH:11]=3)[CH:7]=[N:8][C:4]=2[CH:3]=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:24][C@@H:19]1[CH2:20][CH2:21][CH2:22][CH2:23][C@H:18]1[NH:17][C:15]1[O:16][C:12]2[CH:11]=[C:10]([CH2:9][N:6]3[C:5]4[CH:27]=[CH:28][C:2]([C:30]#[N:31])=[CH:3][C:4]=4[N:8]=[CH:7]3)[CH:26]=[CH:25][C:13]=2[N:14]=1

Komponenten

7

Edukt 3

HCID 962WaterHCID 6228DimethylformamideHCID 86681183(1R,2R)-2-((6-((5-bromo-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol

Produkt 1

HCID 866811841-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]oxazol-6-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrileAusbeute 35,7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

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

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A mixture of (1R,2R)-2-((6-((5-bromo-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol (126 mg, 0.29 mmol), Zn(CN)2 (134 mg, 1.14 mmol), Pd2(dba)3 (53 mg, 0.06 mmol) and dppf (63 mg, 0.12 mmol) in DMF (4 mL) was stirred at 130° C. for 6 h. The reaction mixture was cooled to rt, poured into water (20 mL) and extracted with ethyl acetate (20 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 preparative HPLC to give 1-((2-(((1R,2R)-2-hydroxycyclohexyl)amino)benzo[d]oxazol-6-yl)methyl)-1H-benzo[d]imidazole-5-carbonitrile as a white solid (40 mg, 35.7%). 1H NMR (300 MHz, DMSO-d6) δ 8.67 (s, 1H), 8.20 (s, 1H), 7.83-7.78 (m, 2H), 7.61 (d, J=6.9 Hz, 1H), 7.41 (s, 1H), 7.14 (s, 1H), 5.54 (s, 2H), 4.68 (d, 1H), 3.32 (br s, 2H), 1.91 (br s, 2H), 1.62 (br s, 2H), 1.22 (br s, 4H). LCMS (ESI) m/z 388 (M+H)+.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to rt
  2. extractionextracted with ethyl acetate (20 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 preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-7e0e03b827514ae38d593f0c85e5f738
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08952058B2

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