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Sodium triacetoxyborohydride → 1-{2-[(3R,4S)-4-({[5-chloro-6-(hydroxymethyl)-3-pyridinyl]methyl}amino)-3-hydroxy-1-piperidinyl]ethyl}-7-(methyloxy)-1,5-naphthyridin-2(1H)-one

HRID 1881738
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Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 1881738
[NH2:1][C@H:2]1[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]2[C:19]3[C:14](=[N:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=3)[CH:13]=[CH:12][C:11]2=[O:22])[CH2:4][C@H:3]1[OH:23].[Cl:24][C:25]1[CH:26]=[C:27]([CH:33]=O)[CH:28]=[N:29][C:30]=1[CH2:31][OH:32].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.CO>[Cl:24][C:25]1[CH:26]=[C:27]([CH2:33][NH:1][C@H:2]2[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][N:10]3[C:19]4[C:14](=[N:15][CH:16]=[C:17]([O:20][CH3:21])[CH:18]=4)[CH:13]=[CH:12][C:11]3=[O:22])[CH2:4][C@H:3]2[OH:23])[CH:28]=[N:29][C:30]=1[CH2:31][OH:32]
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Komponenten

6

Edukt 3

HCID 5049666Sodium triacetoxyborohydrideHCID 580017855-Chloro-6-(hydroxymethyl)-3-pyridinecarbaldehydeHCID 585794061-{2-[(3R,4S)-4-amino-3-hydroxy-1-piperidinyl]ethyl}-7-(methyloxy)-1,5-naphthyridin-2(1H)-one

Produkt 1

HCID 468464921-{2-[(3R,4S)-4-({[5-chloro-6-(hydroxymethyl)-3-pyridinyl]methyl}amino)-3-hydroxy-1-piperidinyl]ethyl}-7-(methyloxy)-1,5-naphthyridin-2(1H)-one

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 887MethanolLösungsmittel

Versuchsvorschrift

A mixture of 1-{2-[(3R,4S)-4-amino-3-hydroxy-1-piperidinyl]ethyl}-7-(methyloxy)-1,5-naphthyridin-2(1H)-one (Intermediate 33 as a free base: 200 mg, 0.628 mmol) and 5-chloro-6-(hydroxymethyl)-3-pyridinecarbaldehyde (108 mg, 0.628 mmol) in DCE (10 ml) and Methanol (0.5 ml) was stirred at room temperature overnight. Sodium triacetoxyborohydride (399 mg, 1.885 mmol) was added. The mixture was stirred under N2 at rt for 6 h. LCMS showed imine and desired compound. An excess of sodium triacetoxyborohydride (399 mg, 1.885 mmol) was added. The mixture was stirred overnight. Full conversion to the amine was observed by LCMS. It was quenched with saturated NaHCO3, extracted with DCM/MeOH 9/1, dried (MgSO4), filtered, and concentrated affording 242 mg of crude material. Purification by manual flash chromatography using a 5 g Merck silica gel cartridge, and DCM/MeOH 9/1 as eluent afforded 1-{2-[(3R,4S)-4-({[5-chloro-6-(hydroxymethyl)-3-pyridinyl]methyl}amino)-3-hydroxy-1-piperidinyl]ethyl}-7-(methyloxy)-1,5-naphthyridin-2(1H)-one (179.8 mg, 0.360 mmol, 57% yield) as a white solid.

Quellen und Nachweise

ORD-Eintrag
ord-65cdeb61fb7540cf808e2e649f9d4223
Quelldatensatz
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08318940B2

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