Ethyl N-methoxy-N-methylcarbamate → 3-(5-Fluoro-3-methyl-benzo[b]thiophen-2-yl)-2,6-dimethyl-imidazo[1,2-b]pyridazine-8-carboxylic acid methoxy-methyl-amide

HRID 226115노트

반응식

HRID 226115 반응식
[F:1][C:2]1[CH:22]=[CH:21][C:5]2[S:6][C:7]([C:10]3[N:14]4[N:15]=[C:16]([CH3:19])[CH:17]=[CH:18][C:13]4=[N:12][C:11]=3[CH3:20])=[C:8]([CH3:9])[C:4]=2[CH:3]=1.[CH3:23][O:24][N:25]([CH3:31])[C:26](=O)[O:27]CC.[Li+].CC([N-]C(C)C)C>C1COCC1>[CH3:23][O:24][N:25]([CH3:31])[C:26]([C:18]1[C:13]2[N:14]([C:10]([C:7]3[S:6][C:5]4[CH:21]=[CH:22][C:2]([F:1])=[CH:3][C:4]=4[C:8]=3[CH3:9])=[C:11]([CH3:20])[N:12]=2)[N:15]=[C:16]([CH3:19])[CH:17]=1)=[O:27]

참가 물질

5

반응물 3

HCID 533715Ethyl N-methoxy-N-methylcarbamateHCID 2724682Lithium diisopropylamideHCID 688598503-(5-Fluoro-3-methyl-benzo[b]thiophen-2-yl)-2,6-dimethyl-imidazo[1,2-b]pyridazine

생성물 1

HCID 866210453-(5-Fluoro-3-methyl-benzo[b]thiophen-2-yl)-2,6-dimethyl-imidazo[1,2-b]pyridazine-8-carboxylic acid methoxy-methyl-amide수율 31.7%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-78 °C

실험 절차

The solution of 3-(5-fluoro-3-methyl-benzo[b]thiophen-2-yl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (2.09 g, 6.73 mmol) in THF (56 mL) is stirred at −78° C. Ethyl N-methoxy-N-methylcarbamate (4.48 g, 33.7 mmol) is added. LDA (10 mL, 20.1 mmol) is added dropwise to maintain reaction temperature at −75° C. The reaction is stirred at −78° C. for 1 hour. The mixture is quenched with H2O, filtered through celite with CH2Cl2. The collect solution is washed with H2O, dried over Na2SO4, filtered and concentrated. The crude is purified by ISCO (50-100% EtOAc/Hexane) to give the title compound (0.85 g, 31%). 1H NMR (CDCl3): δ 7.8 (dd, J=4.8, 8.5 Hz, 1H), 7.5 (dd, J=2.5, 9.7 Hz, 1H), 7.2 (m, 1H), 7.0 (s, 1H), 3.7 (s, 3H), 3.5 (s, 3H), 2.6 (s, 3H), 2.55 (s, 3H), 2.3 (s, 3H) ppm. MS (m/e): 399 (100%, M+1).

후처리

  1. temperatureto maintain
  2. customreaction temperature at −75° C
  3. customThe mixture is quenched with H2O
  4. filtrationfiltered through celite with CH2Cl2
  5. washThe collect solution is washed with H2O
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude is purified by ISCO (50-100% EtOAc/Hexane)

출처 및 근거

ORD 기록
ord-8fc792b35b1541978efcda4e44742859
출처 데이터셋
uspto-grants-2009_07
특허 번호
US07557103B2

반응 노트

불러오는 중…