Trimethylsilyl isocyanate → 1-(1-(1-(4-chloro-3-((R)-1-(2,4-dichlorophenyl)ethylamino)phenyl)piperidin-4-yl)pyrrolidin-3-yl)urea

HRID 75140Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 75140
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:18][CH2:17][CH:16]([NH2:19])[CH2:15]3)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[NH:20][C@@H:21]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=1[Cl:30])[CH3:22].C[Si]([N:35]=[C:36]=[O:37])(C)C>C1COCC1.C(O)(=O)C>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([N:14]3[CH2:18][CH2:17][CH:16]([NH:19][C:36]([NH2:35])=[O:37])[CH2:15]3)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[NH:20][C@@H:21]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=1[Cl:30])[CH3:22]

Komponenten

5

Edukt 2

HCID 70696Trimethylsilyl isocyanateHCID 86689059HCID 86689059, Verbindung

Produkt 1

HCID 715818821-(1-(1-(4-chloro-3-((R)-1-(2,4-dichlorophenyl)ethylamino)phenyl)piperidin-4-yl)pyrrolidin-3-yl)ureaAusbeute 26 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidKatalysatorHCID 8028TetrahydrofuranLösungsmittel2×

Versuchsvorschrift

To a stirred solution of 1-(1-(4-chloro-3-((R)-1-(2,4-dichlorophenyl)ethylamino)phenyl)piperidin-4-yl)pyrrolidin-3-amine (0.056 g, 0.12 mmol) in THF (1 mL) and acetic acid (1 drop) was added a solution of (trimethylsily)isocyanate (0.015 g, 0.13 mmol) in THF (0.5 mL). The reaction mixture was stirred at room temperature for 30 min. The reaction mixture was quenched with diluted with aqueous saturated sodium bicarbonate and extracted with EtOAc. The organic layer was dried (Na2SO4), filtered, and concentrated in vacuo. The resulting crude was purified by flash chromatography (SiO2, 2-10% methanol in dichloromethane) to afford the desired product as a white solid (0.016 g, 0.031 mmol, 26%). 1H NMR (400 MHz, CDCl3) δ 7.36-7.32 (m, 2H), 7.16 (dd, J=2.2, 8.4 Hz, 1H), 7.04 (d, J=8.6 Hz, 1H), 6.82 (br, 1H), 6.16 (dd, J=2.5, 8.8 Hz, 1H), 5.77 (br, 1H), 5.23 (br, 1H), 4.87 (q, J=6.6 Hz, 1H), 4.64 (d, J=5.2 Hz, 1H), 3.44-3.37 (m, 2H), 3.08-2.82 (m, 3H), 2.69-2.40 (m, 4H), 2.25-1.85 (m, 6H), 1.60-1.42 (m, 5H); MS: (ES) m/z calculated for C24H31Cl3N5O [M+H]+ 510.2. found 510.

Aufarbeitung

  1. customThe reaction mixture was quenched
  2. additionwith diluted with aqueous saturated sodium bicarbonate
  3. extractionextracted with EtOAc
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude was purified by flash chromatography (SiO2, 2-10% methanol in dichloromethane)

Quellen und Nachweise

ORD-Eintrag
ord-dbe795f1da8e4ec4a62390b96e5cbdbc
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08835419B2

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