1,2-Dimethoxyethane → methyl 6-((2S,4R)-1-acetyl-4-((tert-butoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)nicotinate

HRID 882261Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 882261
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10](B3OC(C)(C)C(C)(C)O3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2].Br[C:33]1[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:35][N:34]=1.C(=O)([O-])[O-].[K+].[K+].COCCOC>CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:33]3[CH:42]=[CH:41][C:36]([C:37]([O:39][CH3:40])=[O:38])=[CH:35][N:34]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:30])[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2]

Komponenten

7

Edukt 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 13349623Methyl 6-bromopyridine-3-carboxylateHCID 86709429Tert-butyl ((2S,4R)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinolin-4-yl)carbamate

Produkt 1

HCID 86709428methyl 6-((2S,4R)-1-acetyl-4-((tert-butoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)nicotinate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 887MethanolLösungsmittel

Versuchsvorschrift

In a separate vial, Tert-butyl ((2S,4R)-1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydroquinolin-4-yl)carbamate (for a preparation see Intermediate 61) (2.2 g, 5.11 mmol), methyl 6-bromonicotinate (1.325 g, 6.13 mmol), Pd(PPh3)4 (0.591 g, 0.511 mmol) and potassium carbonate (2.120 g, 15.34 mmol) were combined in methanol (10 mL) and DME (3 mL) and heated under microwave irradiation to 100° C. for 70 mins. The two reaction mixtures were combined and partitioned between water (150 mL) and DCM (3×150 mL). The aqueous layer was acidified to pH 3 via the addition of aq. HCl and extracted with DCM (3×100 mL). The combined organic layers were dried by passing through a hydrophobic frit, and concentrated in vacuo to give crude methyl 6-((2S,4R)-1-acetyl-4-((tert-butoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)nicotinate (2.2 g) which was used directly in the next step without further purification. LCMS: (Formate, 2 min), Rt=1.06 min, MH+440.

Aufarbeitung

  1. customThe two reaction mixtures
  2. custompartitioned between water (150 mL) and DCM (3×150 mL)
  3. additionThe aqueous layer was acidified to pH 3 via the addition of aq. HCl
  4. extractionextracted with DCM (3×100 mL)
  5. customThe combined organic layers were dried
  6. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-17fcdb140d6444b3842cef5abe19b6f9
Quelldatensatz
uspto-grants-2015_03
Patentnummer
US08993554B2

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