1,2-Dichloroethane → 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-N-(2-hydroxyethyl)benzamide

HRID 882279Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 882279
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:22]=[CH:21][C:17]([C:18]([OH:20])=O)=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[CH:26][N:25]=2)[CH2:6][C@@H:5]1[CH3:32])(=[O:3])[CH3:2].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.Cl.C([N:50]1CC[O:53][CH2:52][CH2:51]1)C.NCCO.C1C=CC2N(O)N=NC=2C=1>CN(C=O)C>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[CH:16][C:17]([C:18]([NH:50][CH2:51][CH2:52][OH:53])=[O:20])=[CH:21][CH:22]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]#[N:31])=[CH:26][N:25]=2)[CH2:6][C@@H:5]1[CH3:32])(=[O:3])[CH3:2]

Komponenten

8

Edukt 6

HCID 111,2-Dichloroethane2×HCID 700Ethanolamine2×HCID 7525Ethylmorpholine2×HCID 757711-HydroxybenzotriazoleHCID 22729017HOBT hydrochlorideHCID 709764624-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid

Produkt 1

HCID 714676024-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-N-(2-hydroxyethyl)benzamideAusbeute 8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

A solution of 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid (for a preparation see Intermediate 4) (90 mg, 0.211 mmol) in DMF (2 mL) was treated with EDC (48.5 mg, 0.253 mmol), HOBT hydrochloride (38.8 mg, 0.253 mmol) and N-ethylmorpholine (0.080 mL, 0.633 mmol) and after 3 min with 2-aminoethanol (0.025 mL, 0.422 mmol)). The resulting mixture was stirred at room temperature for 5 h then EDC (48.5 mg, 0.253 mmol), N-ethyl morpholine (0.080 mL, 0.633 mmol), HOBT (38.8 mg, 0.253 mmol) and further 2-aminoethanol (0.025 mL, 0.422 mmol) were added and the corresponding mixture was stirred for 16 h then concentrated in vacuo. The residue was partitioned between water and EtOAc and the layers were separated. The aqueous phase was extracted with EtOAc (×2) and the combined organic layers were washed with saturated aqueous NaHCO3 (×3), then brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by MDAP to give 4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-N-(2-hydroxyethyl)benzamide (8 mg, 8%) as a white solid. LCMS (HpH, 2 min), Rt=0.78 min, MH+=470.

Aufarbeitung

  1. stirringthe corresponding mixture was stirred for 16 h
  2. concentrationthen concentrated in vacuo
  3. customThe residue was partitioned between water and EtOAc
  4. customthe layers were separated
  5. extractionThe aqueous phase was extracted with EtOAc (×2)
  6. washthe combined organic layers were washed with saturated aqueous NaHCO3 (×3)
  7. dry with materialbrine, dried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by MDAP

Quellen und Nachweise

ORD-Eintrag
ord-21ead38fed1d423fad5176be1f4604e8
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08993554B2

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