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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
ノート
印刷プレビュー

反応式

HRID 1881738 の反応式
[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]
参加物実験手順出典と根拠反応ノート

参加物

6

反応物 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

生成物 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

試薬・触媒・溶媒 2

HCID 11
1,2-Dichloroethane
溶媒
HCID 887Methanol溶媒

実験手順

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.

出典と根拠

ORDレコード
ord-65cdeb61fb7540cf808e2e649f9d4223
出典データセット
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08318940B2

反応ノート

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