Water → (1R,2R)-2-((6-((6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol

HRID 1848176Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1848176
[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[CH:9][N:8]([CH2:11][C:12]3[CH:23]=[CH:22][C:15]4[N:16]=[C:17](S(C)=O)[O:18][C:14]=4[CH:13]=3)[C:7]=2[CH:24]=1.[NH2:25][C@@H:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]1[OH:32].CCN(C(C)C)C(C)C.O>CC(N(C)C)=O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[N:10]=[CH:9][N:8]([CH2:11][C:12]3[CH:23]=[CH:22][C:15]4[N:16]=[C:17]([NH:25][C@@H:26]5[CH2:31][CH2:30][CH2:29][CH2:28][C@H:27]5[OH:32])[O:18][C:14]=4[CH:13]=3)[C:7]=2[CH:24]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 735777(1R,2R)-2-AminocyclohexanolHCID 866811456-((6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)-2-(methylsulfinyl)benzo[d]oxazole

Produkt 1

HCID 86681146(1R,2R)-2-((6-((6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanolAusbeute 29 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 31374DimethylacetamideLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

A mixture of 6-((6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)-2-(methyl sulfinyl)benzo[d]oxazole (595 mg, 1.74 mmol), (1R,2R)-2-aminocyclohexanol (301 mg, 2.6 mmol) and DIEA (449 mg, 3.48 mmol) in DMA (12 mL) was stirred at 120° C. for 1.5 h. The reaction mixture was cooled to rt, poured into water (30 mL) and extracted with ethyl acetate (30 mL×3). The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by preparative HPLC to give (1R,2R)-2-((6-((6-methoxy-1H-benzo[d]imidazol-1-yl)methyl)benzo[d]oxazol-2-yl)amino)cyclohexanol as a white solid (198 mg, 29.0%). 1H NMR (300 MHz, DMSO-d6) δ 8.24 (s, 1H), 7.80 (d, J=6.9 Hz, 1H), 7.50 (d, J=8.7 Hz, 1H), 7.36 (s, 1H), 7.14 (s, 3H), 6.80 (dd, J=2.4, 9.0 Hz, 1H), 5.42 (s, 2H), 4.68 (d, J=3.3 Hz, 1H), 3.76 (s, 3H), 3.33 (br s, 2H), 1.89 (br s, 2H), 1.62 (br s, 2H), 1.22 (br s, 4H). LCMS (ESI) m/z 393 (M+H)+.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to rt
  2. extractionextracted with ethyl acetate (30 mL×3)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by preparative HPLC

Quellen und Nachweise

ORD-Eintrag
ord-0290dee6962a4aa1ad9bd2b2fea9b14a
Quelldatensatz
uspto-grants-2015_02
Patentnummer
US08952058B2

Notizen zur Reaktion

Wird geladen…