Dimethyl malonate → Methyl 4-amino-2-methyl-3-[3-(methyloxy)phenyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylate

HRID 573560ノート

反応式

HRID 573560 の反応式
[NH2:1][C:2]1[S:3][C:4]([CH3:17])=[C:5]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[CH:10]=2)[C:6]=1[C:7]#[N:8].[C:18](OC)(=[O:24])[CH2:19][C:20]([O:22][CH3:23])=[O:21].Cl[Sn](Cl)(Cl)Cl>C1(C)C=CC=CC=1>[NH2:8][C:7]1[C:6]2[C:5]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([O:15][CH3:16])[CH:10]=3)=[C:4]([CH3:17])[S:3][C:2]=2[NH:1][C:18](=[O:24])[C:19]=1[C:20]([O:22][CH3:23])=[O:21]

参加物

5

反応物 3

HCID 7943Dimethyl malonateHCID 24287Tin tetrachlorideHCID 672368862-Amino-5-methyl-4-[3-(methyloxy)phenyl]-3-thiophenecarbonitrile

生成物 1

HCID 68323874Methyl 4-amino-2-methyl-3-[3-(methyloxy)phenyl]-6-oxo-6,7-dihydrothieno[2,3-b]pyridine-5-carboxylate収率 41%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒

実験手順

To a solution of 2-amino-5-methyl-4-[3-(methyloxy)phenyl]-3-thiophene carbonitrile (Description 3) (2.80 g, 11.46 mmol) in toluene (75 mL) was added dimethyl malonate (1.31 mL, 11.46 mmol) and SnCl4 (2.68 mL, 22.92 mmol). The reaction mixture was then refluxed under nitrogen for ca. 2 h. The reaction mixture was then cooled to RT and concentrated in vacuo. The residue was partitioned between water and ethyl acetate (ca. 150 mL each) and the organic layer separated and washed with water (ca. 100 mL). The combined aqueous layer was re-extracted with ethyl acetate (ca. 100 mL). All organic layers were combined and passed through a phase separator and the mixture concentrated in vacuo. The residue was purified by normal phase chromatography, eluting with a gradient of 0-60% ethyl acetate in DCM followed by 0-20% MeOH in DCM, to afford the title compound (1.62 g). LCMS (A) m/z: 343 [M−1]−, Rt 1.18 min (acidic).

後処理

  1. temperatureThe reaction mixture was then refluxed under nitrogen for ca. 2 h
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between water and ethyl acetate (ca. 150 mL each)
  4. customthe organic layer separated
  5. washwashed with water (ca. 100 mL)
  6. extractionThe combined aqueous layer was re-extracted with ethyl acetate (ca. 100 mL)
  7. concentrationthe mixture concentrated in vacuo
  8. customThe residue was purified by normal phase chromatography
  9. washeluting with a gradient of 0-60% ethyl acetate in DCM

出典と根拠

ORDレコード
ord-f673c1b0b8af498ea9338dfc0a037172
出典データセット
uspto-grants-2015_05
特許番号
US09029545B2

反応ノート

読み込み中…