4-Methylmorpholine → (R)-methyl 3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)benzoate

HRID 59905Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 59905
Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH:11]=[CH:12][CH:13]=1)[C:7]([O:9][CH3:10])=[O:8].CN1CCOCC1.CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.[CH2:43]([O:45][C:46]1[CH:67]=[CH:66][CH:65]=[CH:64][C:47]=1[O:48][C@@H:49]1[CH2:54][CH2:53][CH2:52][N:51]([C:55]2[N:60]=[CH:59][C:58]([C:61](O)=[O:62])=[CH:57][N:56]=2)[CH2:50]1)[CH3:44]>C1COCC1.CS(C)=O>[CH2:43]([O:45][C:46]1[CH:67]=[CH:66][CH:65]=[CH:64][C:47]=1[O:48][C@@H:49]1[CH2:54][CH2:53][CH2:52][N:51]([C:55]2[N:60]=[CH:59][C:58]([C:61]([NH:2][CH2:3][C:4]3[CH:5]=[C:6]([CH:11]=[CH:12][CH:13]=3)[C:7]([O:9][CH3:10])=[O:8])=[O:62])=[CH:57][N:56]=2)[CH2:50]1)[CH3:44]

Komponenten

8

Edukt 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2794825Methyl 3-(aminomethyl)benzoate HydrochlorideHCID 118366221(R)-2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxylic acid

Produkt 1

HCID 118366276(R)-methyl 3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)benzoateAusbeute 74,5 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 679Dimethyl SulfoxideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
15 °C

Versuchsvorschrift

To a 500-mL 3-neck flask was added methyl 3-(aminomethyl)benzoate hydrochloride (12.9 g, 64.1 mmol) followed by DMSO (26 mL). The solution was cooled to 15° C. N-Methyl morpholine (27 mL, 240 mmol) was added followed by EDCl (13 g, 68 mmol) and HOBT (4.09 g, 30 mmol), maintaining the temperature at 15° C. A solution of (R)-2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxylic acid (20.94 g, 60.98 mmol) in THF (100 mL) was added dropwise over 10 min. The reaction mixture was warmed to 20-25° C. and stirred for 4 hours. The reaction mixture was concentrated under reduced pressure, and the residue was partitioned between water (200 mL) and pentane-ethyl acetate (1:2, 300 mL). The aqueous phase was further extracted with ethyl acetate (2 times with 100 mL). The combined organic extracts were rinsed sequentially with water (200 mL), saturated aqueous sodium bicarbonate solution (2 times with 100 mL), and brine (2 times with 25 mL). The organic layer was then dried over sodium sulfate, filtered, and concentrated to afford (R)-methyl 3-((2-(3-(2-ethoxyphenoxy)piperidin-1-yl)pyrimidine-5-carboxamido)methyl)benzoate (22.3 g). MS (ES+) 491.3 (M+H).

Aufarbeitung

  1. temperaturemaintaining the temperature at 15° C
  2. temperatureThe reaction mixture was warmed to 20-25° C.
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. customthe residue was partitioned between water (200 mL) and pentane-ethyl acetate (1:2, 300 mL)
  5. extractionThe aqueous phase was further extracted with ethyl acetate (2 times with 100 mL)
  6. washThe combined organic extracts were rinsed sequentially with water (200 mL), saturated aqueous sodium bicarbonate solution (2 times with 100 mL), and brine (2 times with 25 mL)
  7. dry with materialThe organic layer was then dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-3980f80b95d54813af43c984dd55e2ae
Quelldatensatz
uspto-grants-2016_09
Patentnummer
US09440949B2

Notizen zur Reaktion

Wird geladen…