ホームMCPワークベンチSkills
ホームワークベンチ通知マイページ
llms.txt · MCPガイドプライバシーポリシー · 利用規約 · サポートv1.8.0
  1. ホーム
  2. /反応

Diisopropylethylamine → 4-(((1R,3S)-3-hydroxy-3-methylcyclohexyl)amino)-2-(methylthio)pyrimidine-5-carbonitrile

HRID 1749505
ノート
印刷プレビュー

反応式

HRID 1749505 の反応式
Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]([S:10][CH3:11])[N:3]=1.[NH2:12][CH:13]1[CH2:18][CH2:17][CH2:16][C:15]([CH3:20])([OH:19])[CH2:14]1.CCN(C(C)C)C(C)C>C(O)(C)C>[OH:19][C@:15]1([CH3:20])[CH2:16][CH2:17][CH2:18][C@H:13]([NH:12][C:2]2[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]([S:10][CH3:11])[N:3]=2)[CH2:14]1.[OH:19][C@@:15]1([CH3:20])[CH2:16][CH2:17][CH2:18][C@@H:13]([NH:12][C:2]2[C:7]([C:8]#[N:9])=[CH:6][N:5]=[C:4]([S:10][CH3:11])[N:3]=2)[CH2:14]1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

6

反応物 3

HCID 81531DiisopropylethylamineHCID 131141834-Chloro-2-(methylsulfanyl)pyrimidine-5-carbonitrileHCID 134950983-Amino-1-methylcyclohexan-1-ol

生成物 2

HCID 1181620774-(((1S,3R)-3-hydroxy-3-methylcyclohexyl)amino)-2-(methylthio)pyrimidine-5-carbonitrile収率 33%HCID 1181622264-(((1R,3S)-3-hydroxy-3-methylcyclohexyl)amino)-2-(methylthio)pyrimidine-5-carbonitrile
収率 34%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
100 °C

実験手順

A mixture of 4-chloro-2-(methylthio)pyrimidine-5-carbonitrile (3.71 g, 20 mmol)), 3-amino-1-methylcyclohexanol (3.0 g, crude), DIEA (3.23 g, 25 mmol) in isopropanol (30 mL) was heated at 100° C. for 3 h. The organic solvents were removed under reduced pressure. The residue was treated with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate and concentrated to give the crude product, which was purified by silica gel column chromatography (20% ethyl acetate in petroleum) to afford the cis-isomer (0.90 g, 3.24 mmol, 17% yield over 3 steps) and trans-isomer (1.80 g, 6.47 mmol, 34% yield over 3 steps). The cis-isomer (0.90 g, 3.24 mmol) was separated by chiral SFC (Column IF; method: 70-30-CO2-MeOH; CO2 Flow Rate: 2.1; Col. Temp.=40° C.) to give 4-(((1S,3R)-3-hydroxy-3-methylcyclohexyl)amino)-2-(methylthio)pyrimidine-5-carbonitrile (peak 1: 300 mg, 1.08 mmol, 33% yield, 100% e.e.) and 4-(((1R,3S)-3-hydroxy-3-methylcyclohexyl)amino)-2-(methylthio)pyrimidine-5-carbonitrile (peak 2: 310 mg, 1.12 mmol, 34% yield, 100% e.e.), MS (ESI) m/z 279.1 [M+H]+.

後処理

  1. customThe organic solvents were removed under reduced pressure
  2. additionThe residue was treated with water
  3. extractionextracted with ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customto give the crude product, which
  8. customwas purified by silica gel column chromatography (20% ethyl acetate in petroleum)
  9. customto afford the cis-isomer (0.90 g, 3.24 mmol, 17% yield over 3 steps) and trans-isomer (1.80 g, 6.47 mmol, 34% yield over 3 steps)
  10. customThe cis-isomer (0.90 g, 3.24 mmol) was separated by chiral SFC (Column IF; method: 70-30-CO2-MeOH; CO2 Flow Rate: 2.1; Col. Temp.=40° C.)

出典と根拠

ORDレコード
ord-7bac73e6d320436ba0d8d585dcae9dcd
出典データセット
uspto-grants-2015_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09156798B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート