(2R)-2-hydroxypropanamide → HCID 178462237, Verbindung

HRID 711975Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 711975
[OH:1][C@H:2]([CH3:6])[C:3]([NH2:5])=O.F[B-](F)(F)F.C([O+](CC)CC)C.N[C:20]1[C:21]([NH:29][C@H:30]2[CH2:35][CH2:34][C@H:33]([CH2:36][C:37]#[N:38])[CH2:32][CH2:31]2)=[C:22]2[S:28][CH:27]=[CH:26][C:23]2=[N:24][CH:25]=1>O1CCCC1.C(O)C>[OH:1][C@@H:2]([C:3]1[N:29]([C@H:30]2[CH2:31][CH2:32][C@H:33]([CH2:36][C:37]#[N:38])[CH2:34][CH2:35]2)[C:21]2=[C:22]3[S:28][CH:27]=[CH:26][C:23]3=[N:24][CH:25]=[C:20]2[N:5]=1)[CH3:6]

Komponenten

6

Edukt 3

HCID 1530236(2R)-2-hydroxypropanamideHCID 2723982Triethyloxonium tetrafluoroborateHCID 178511084HCID 178511084, Verbindung

Produkt 1

HCID 178462237HCID 178462237, VerbindungAusbeute 73,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 702EthanolLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

A mixture of (2R)-2-hydroxypropanamide (0.630 g, 7.07 mmol) and triethyloxonium tetrafluoroborate (1.26 g, 6.66 mmol) in tetrahydrofuran (9.7 mL) was stirred at room temperature for 2 h. The solvent was removed, and the residue dissolved in ethanol (4.1 mL) and added to a suspension of {trans-4-[(6-aminothieno[3,2-b]pyridin-7-yl)amino]cyclohexyl}acetonitrile (0.63 g, 2.2 mmol) in ethanol (15 mL). The reaction was stirred at 80° C. for 2 h. The solvent was removed and the residue was partitioned between EtOAc and sat. NaHCO3 solution. The organic phase was washed with brine, dried over MgSO4, and concentrated. The residue was purified on silica gel (eluting with 0 to 10% MeOH in dichloromethane), then further purified on RP-HPLC (XBridge C18 column, eluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min) to give the desired product (0.55 g, 73%). LCMS calculated for C18H21N4OS (M+H)+: m/z=341.1. Found: 341.1.

Aufarbeitung

  1. customThe solvent was removed
  2. dissolutionthe residue dissolved in ethanol (4.1 mL)
  3. stirringThe reaction was stirred at 80° C. for 2 h
  4. customThe solvent was removed
  5. customthe residue was partitioned between EtOAc and sat. NaHCO3 solution
  6. washThe organic phase was washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customThe residue was purified on silica gel (eluting with 0 to 10% MeOH in dichloromethane)
  10. customfurther purified on RP-HPLC (XBridge C18 column
  11. washeluting with a gradient of acetonitrile/water containing 0.1% ammonium hydroxide, at flow rate of 30 mL/min)

Quellen und Nachweise

ORD-Eintrag
ord-de481c3227e246d6a9935c8f2e9265fe
Quelldatensatz
uspto-grants-2015_11
Patentnummer
US09181271B2

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