Water → 2-{(3S)-3-[(2-{[tert-Butyl(dimethyl)silyl]oxy}ethyl)amino]pyrrolidin-1-yl}-6-chloro-N-[(1-hydroxycycloheptyl)methyl]quinoline-5-carboxamide

HRID 424766ノート

反応式

HRID 424766 の反応式
[NH2:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:16]=[CH:15][C:14]3[C:13]([C:17]([NH:19][CH2:20][C:21]4([OH:28])[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]4)=[O:18])=[C:12]([Cl:29])[CH:11]=[CH:10][C:9]=3[N:8]=2)[CH2:3]1.[CH3:30][C:31]([Si:34]([CH3:40])([CH3:39])[O:35][CH2:36][CH:37]=O)([CH3:33])[CH3:32].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].O>ClCCl>[Si:34]([O:35][CH2:36][CH2:37][NH:1][C@H:2]1[CH2:6][CH2:5][N:4]([C:7]2[CH:16]=[CH:15][C:14]3[C:13]([C:17]([NH:19][CH2:20][C:21]4([OH:28])[CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]4)=[O:18])=[C:12]([Cl:29])[CH:11]=[CH:10][C:9]=3[N:8]=2)[CH2:3]1)([C:31]([CH3:33])([CH3:32])[CH3:30])([CH3:40])[CH3:39]

参加物

6

反応物 4

HCID 962WaterHCID 41877882-((Tert-butyldimethylsilyl)oxy)acetaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 577339902-[(3S)-3-Aminopyrrolidin-1-yl]-6-chloro-N-[(1-hydroxycycloheptyl)methyl]-quinoline-5-carboxamide

生成物 1

HCID 577339922-{(3S)-3-[(2-{[tert-Butyl(dimethyl)silyl]oxy}ethyl)amino]pyrrolidin-1-yl}-6-chloro-N-[(1-hydroxycycloheptyl)methyl]quinoline-5-carboxamide

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

2-[(3S)-3-Aminopyrrolidin-1-yl]-6-chloro-N-[(1-hydroxycycloheptyl)methyl]-quinoline-5-carboxamide (17.6 g) was suspended in dichloromethane (300 ml) and molecular sieves (17.6 g) were added under a nitrogen atmosphere. [[(1,1-dimethylethyl)-dimethylsilyl]-oxy]acetaldehyde (7.2 ml) was added dropwise with stirring over 5 minutes and the mixture was stirred at room temperature for 6 hours. Sodium triacetoxyborohydride (17.9 g) was added in one portion and the mixture was stirred at room temperature for a further 17 hours before water (10 ml) was added, the mixture was stirred at room temperature for 30 minutes, concentrated onto silica in vacuo and purified by flash column chromatography (SiO2, 1:2:97-1:8:91 7M NH3 in methanol:methanol:dichloromethane as gradient elution) to afford the subtitle product as a colourless solid (16.0 g). Impure fractions (4.1 g) were repurified by flash column chromatography (SiO2, 1:2:97-1:8:91 7M NH3 in methanol:methanol:dichloromethane as gradient elution) to afford a second crop of the subtitle product (2.8 g).

後処理

  1. additionmolecular sieves (17.6 g) were added under a nitrogen atmosphere
  2. stirringthe mixture was stirred at room temperature for 6 hours
  3. additionwas added
  4. stirringthe mixture was stirred at room temperature for 30 minutes
  5. concentrationconcentrated onto silica in vacuo
  6. custompurified by flash column chromatography (SiO2, 1:2:97-1:8:91 7M NH3 in methanol:methanol:dichloromethane as gradient elution)

出典と根拠

ORDレコード
ord-43be8ed82a9f4b04a23863c77e32edab
出典データセット
uspto-grants-2012_01
特許番号
US08106073B2

反応ノート

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