Lithium Chloride → Ethyl 2-(2-acetamidopyridin-4-yl)-4-bromothiazole-5-carboxylate

HRID 2401845노트

반응식

HRID 2401845 반응식
Br[C:2]1[S:3][C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:5]([Br:7])[N:6]=1.C[Sn](C)(C)[C:15]1[CH:20]=[CH:19][N:18]=[C:17]([NH:21][C:22](=[O:24])[CH3:23])[CH:16]=1.[Cl-].[Li+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[C:22]([NH:21][C:17]1[CH:16]=[C:15]([C:2]2[S:3][C:4]([C:8]([O:10][CH2:11][CH3:12])=[O:9])=[C:5]([Br:7])[N:6]=2)[CH:20]=[CH:19][N:18]=1)(=[O:24])[CH3:23]

참가 물질

7

반응물 3

HCID 433294Lithium ChlorideHCID 59529632N-(4-(trimethylstannyl)pyridin-2-yl)acetamideHCID 66747450Ethyl 2,4-dibromothiazole-5-carboxylate

생성물 1

HCID 66747706Ethyl 2-(2-acetamidopyridin-4-yl)-4-bromothiazole-5-carboxylate수율 53%

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418397HCID 178418397, 화합물촉매HCID 312751,4-Dioxane용매

실험 절차

A mixture of ethyl 2,4-dibromothiazole-5-carboxylate (0.500 g, 1.59 mmol), N-(4-(trimethylstannyl)pyridin-2-yl)acetamide (0.569 g, 1.90 mmol), tetrakis(triphenylphosphine)palladium(0) (91.7 mg, 0.0794 mmol), copper(I) iodide (90.7 mg, 0.476 mmol), and lithium chloride (202 mg, 4.76 mmol) in dioxane (29.1 mL) was degassed with nitrogen and heated at reflux for 1 hr. The reaction was cooled and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate/hexane=0/100→50/50) to give 312 mg of the title compound. (44% yield). LC/MS (FA) ES+ 370, 372. 1H NMR (400 MHz, CDCl3) δ: 8.71 (s, 1H), 8.39 (d, 1H, J=5.2 Hz), 8.25 (bs, 1H), 7.68 (dd, 1H, J=5.2, 1.6 Hz), 4.41 (q, 2H, J=7.2 Hz), 2.26 (s, 3H), 1.41 (t, 3H, J=7.2 Hz).

후처리

  1. customwas degassed with nitrogen
  2. temperatureheated
  3. temperatureat reflux for 1 hr
  4. temperatureThe reaction was cooled
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (ethyl acetate/hexane=0/100→50/50)

출처 및 근거

ORD 기록
ord-bff9a28e09cc4ef7a802dcaa954f5161
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08796268B2

반응 노트

불러오는 중…