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

HRID 573560노트

반응식

HRID 573560 반응식
[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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 1140Toluene용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-f673c1b0b8af498ea9338dfc0a037172
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09029545B2

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