Potassium Iodide → (2R,5S)-4-{2-[6-(4-Fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester

HRID 1475521Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1475521
Cl.Cl[CH2:3][C:4]([N:6]1[C:14]2[C:9](=[N:10][CH:11]=[C:12]([CH2:15][C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[CH:13]=2)[C:8]([CH3:24])([CH3:23])[CH2:7]1)=[O:5].[C:25]([O:29][C:30]([N:32]1[CH2:37][C@H:36]([CH2:38][N:39]2[CH2:44][CH2:43][O:42][CH2:41][C@H:40]2[CH3:45])[NH:35][CH2:34][C@H:33]1[CH3:46])=[O:31])([CH3:28])([CH3:27])[CH3:26].C(=O)([O-])[O-].[K+].[K+].[I-].[K+]>C(#N)C.O>[C:25]([O:29][C:30]([N:32]1[CH2:37][C@H:36]([CH2:38][N:39]2[CH2:44][CH2:43][O:42][CH2:41][C@H:40]2[CH3:45])[N:35]([CH2:3][C:4]([N:6]2[C:14]3[C:9](=[N:10][CH:11]=[C:12]([CH2:15][C:16]4[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=4)[CH:13]=3)[C:8]([CH3:24])([CH3:23])[CH2:7]2)=[O:5])[CH2:34][C@H:33]1[CH3:46])=[O:31])([CH3:28])([CH3:26])[CH3:27]

Komponenten

7

Edukt 4

HCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 70980298(2R,5S)-tert-butyl 2-methyl-5-(((R)-3-methylmorpholino)methyl)piperazine-1-carboxylateHCID 867240432-Chloro-1-[6-(4-fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-ethanone hydrochloride

Produkt 1

HCID 70980911(2R,5S)-4-{2-[6-(4-Fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-2-oxo-ethyl}-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl esterAusbeute 103,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittel

Reaktionsbedingungen

Temperatur
20 °C

Versuchsvorschrift

A mixture of 2-chloro-1-[6-(4-fluoro-benzyl)-3,3-dimethyl-2,3-dihydro-pyrrolo[3,2-b]pyridin-1-yl]-ethanone hydrochloride (6.63 g, 17.96 mmol), (2R,5S)-2-methyl-5-((R)-3-methyl-morpholin-4-ylmethyl)-piperazine-1-carboxylic acid tert-butyl ester (5.62 g, 17.96 mmol), potassium carbonate (9.95 g, 72 mmol) and finely ground potassium iodide (5.98 g, 36 mmol) in acetonitrile (40 mL) was stirred at 20° C. for 1 h. Water (200 mL) was added and mixture stirred for 0.2 h, then the mixture was extracted with EtOAc (200 mL). The organic phase was dried (Na2SO4) and evaporated in vacuo to give the title compound (11.3 g) as an oil, used without further purification. 1H NMR (Me-d3-OD): 8.28-8.19 (1H, m), 8.13-8.04 (1H, m), 7.25 (2H, dd), 7.04 (2H, t), 4.23-4.13 (1H, m), 4.13-4.04 (2H, m), 4.04-3.95 (3H, m), 3.81-3.58 (4H, m), 3.54 (1H, d), 3.25 (2H, dd), 3.01-2.66 (4H, m), 2.62-2.42 (2H, m), 2.42-2.17 (2H, m), 1.47 (9H, s), 1.43-1.37 (6H, m), 1.29-1.21 (3H, m), 1.01 (3H, d). MS: [M+H]+=610. IR: vC═O 1685, 1653 cm−1.

Aufarbeitung

  1. stirringmixture stirred for 0.2 h
  2. extractionthe mixture was extracted with EtOAc (200 mL)
  3. dry with materialThe organic phase was dried (Na2SO4)
  4. customevaporated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-72b89d958b8d41faabd5f723063801ea
Quelldatensatz
uspto-grants-2015_04
Patentnummer
US09018214B2

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