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

Dimethylformamide → (1S,2S)-2-fluoro-N-(7-(5-fluoro-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide

HRID 468935
ノート
印刷プレビュー

反応式

HRID 468935 の反応式
[F:1][C:2]1[C:3]([CH3:19])=[C:4]([C:8]2[CH:17]=[C:16]3[C:11]([CH:12]=[C:13]([NH2:18])[N:14]=[CH:15]3)=[CH:10][CH:9]=2)[CH:5]=[N:6][CH:7]=1.[F:20][C@H:21]1[CH2:23][C@H:22]1[C:24](O)=[O:25].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2N=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.CN(C)C=O>CN(C)C1C=CN=CC=1.C(OCC)(=O)C>[F:20][C@H:21]1[CH2:23][C@H:22]1[C:24]([NH:18][C:13]1[N:14]=[CH:15][C:16]2[C:11]([CH:12]=1)=[CH:10][CH:9]=[C:8]([C:4]1[CH:5]=[N:6][CH:7]=[C:2]([F:1])[C:3]=1[CH3:19])[CH:17]=2)=[O:25]
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

8

反応物 5

HCID 6228DimethylformamideHCID 81531DiisopropylethylamineHCID 9793716cis-2-Fluorocyclopropanecarboxylic acidHCID 11038641((7-Azabenzotriazol-1-YL)oxy)tris(pyrrolidino)phosphonium hexafluorophosphateHCID 679748447-(5-Fluoro-4-methylpyridin-3-yl)isoquinolin-3-amine

生成物 1

HCID 71114972
(1S,2S)-2-fluoro-N-(7-(5-fluoro-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide
収率 57.3%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
40 °C

実験手順

A mixture of 7-(5-fluoro-4-methylpyridin-3-yl)isoquinolin-3-amine (161.4 mg; 0.6372 mmol), (1S,2S)-2-fluorocyclopropanecarboxylic acid (80.3 mg; 0.772 mmol), (7-azabenzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate (496.9 mg; 0.9149 mmol), N,N-diisopropylethylamine (0.30 mL; 1.7 mmol), 4-(dimethylamino)pyridine (0.06372 mmol) and N,N-dimethylformamide (5 mL; 64.4 mmol) was heated at 40° C. for 16 hours. The reaction mixture was diluted with ethyl acetate, washed with water and brine, dried over magnesium sulfate, filtered, and evaporated in vacuo. The crude product was purified via flash chromatography on silica gel (25 g silica, solvent gradient: 30-90% ethyl acetate in dichloromethane) followed by preparatory reverse-phase HPLC to yield 124 mg (57%) of the title compound. LCMS (ESI): RT (min)=8.33, M+H=340.2, method=G; 1H NMR (400 MHz, DMSO) δ 10.99 (s, 1H), 9.21 (s, 1H), 8.55 (d, J=4.5 Hz, 2H), 8.42 (s, 1H), 8.13 (s, 1H), 8.01 (d, J=8.6 Hz, 1H), 7.78 (dd, J=8.5, 1.6 Hz, 1H), 5.06-4.85 (m, 1H), 2.34-2.27 (m, 1H), 2.26 (d, J=1.9 Hz, 3H), 1.75-1.65 (m, 1H), 1.25-1.16 (m, 1H).

後処理

  1. washwashed with water and brine
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. customevaporated in vacuo
  5. customThe crude product was purified via flash chromatography on silica gel (25 g silica, solvent gradient: 30-90% ethyl acetate in dichloromethane)

出典と根拠

ORDレコード
ord-a24a0262b71740a482f7e5981f199a73
出典データセット
uspto-grants-2014_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08623889B2

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