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Malonic Acid → N1-(3-fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide

HRID 1676242
ノート
印刷プレビュー

反応式

HRID 1676242 の反応式
[F:1][C:2]1[CH:3]=[C:4]([NH2:18])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[CH:16][S:17][C:10]=12.[F:19][C:20]1[CH:25]=[CH:24][C:23]([NH:26][C:27](=[O:32])[CH2:28][C:29](O)=[O:30])=[CH:22][CH:21]=1.C(O)(=O)CC(O)=O.FC1C=CC(N)=CC=1.CCN=C=NCCCN(C)C>CCOC(C)=O.C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([NH:18][C:29](=[O:30])[CH2:28][C:27]([NH:26][C:23]2[CH:24]=[CH:25][C:20]([F:19])=[CH:21][CH:22]=2)=[O:32])[CH:5]=[CH:6][C:7]=1[O:8][C:9]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:15]=[CH:16][S:17][C:10]=12
参加物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 867Malonic AcidHCID 97314-FluoroanilineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 43418433-(4-Fluorophenylamino)-3-oxopropanoic acidHCID 594244303-Fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)aniline

生成物 1

HCID 24983260N1-(3-fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)phenyl)-N3-(4-fluorophenyl)malonamide
収率 11%

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a stirred mixture of 3-fluoro-4-(thieno[3,2-b]pyridin-7-yloxy)benzenamine (Example 1-B; 26 mg, 0.10 mmol), 3-(4-fluorophenylamino)-3-oxopropanoic acid (22 mg, 0.11 mmol; prepared from malonic acid and 4-fluoroaniline according to the methods described in WO 2005/030140 and by Shih and Rankin, Synth. Comm. 1996, 26(4), 833-836), and CH2Cl2 (1 mL) was added EDCI (38 mg, 0.20 mmol). The reaction was stirred at room temperature for 2 days. The mixture was diluted with EtOAc (10 mL) and washed with water (3×5 mL), brine (5 mL), dried (Na2SO4), filtered, and concentrated. The crude was purified on a pre-packed Isoelute silica gel column (10 g silica), eluting with a gradient of 20% EtOAc/hexanes, 1:1 EtOAc/hexanes, 2:1 EtOAc/hexanes, and then neat EtOAc. The product was obtained as a waxy solid (5 mg, 11%). 1H NMR (400 MHz, CDCl3) δ 9.57 (s, 1H), 9.10 (s, 1H), 8.52 (m, 1H), 7.80 (m, 2H), 7.57 (m, 3H), 7.27 (m, 2H), 7.04 (m, 2H), 6.53 (d, J=4 Hz, 1H), 3.52 (s, 2H). LRMS (ESI pos) m/e 440 (M+1). HPLC: 97% purity (220 nm).

後処理

  1. washwashed with water (3×5 mL), brine (5 mL)
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude was purified on a pre-packed Isoelute silica gel column (10 g silica)
  6. washeluting with a gradient of 20% EtOAc/hexanes, 1:1 EtOAc/hexanes, 2:1 EtOAc/hexanes

出典と根拠

ORDレコード
ord-5470c80627494c03b5f59e2c25c101b0
出典データセット
uspto-grants-2011_08
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08003662B2

反応ノート

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