5-Bromo-1,2,3-trimethoxybenzene → (2-(1H-indol-5-yl)thiazol-4-yl)(3,4,5-trimethoxyphenyl)methanone

HRID 572462노트

반응식

HRID 572462 반응식
[Li]CCCC.[CH3:6][O:7][C:8]1[CH:9]=[C:10](Br)[CH:11]=[C:12]([O:16][CH3:17])[C:13]=1[O:14][CH3:15].CON(C)[C:22]([C@@H:24]1[CH2:28][S:27][C:26]([C:29]2[CH:30]=[C:31]3[C:35](=[CH:36][CH:37]=2)[N:34](S(C2C=CC=CC=2)(=O)=O)[CH:33]=[CH:32]3)=[N:25]1)=[O:23]>C1COCC1.[OH-].[Na+].C(O)C>[NH:34]1[C:35]2[C:31](=[CH:30][C:29]([C:26]3[S:27][CH:28]=[C:24]([C:22]([C:10]4[CH:9]=[C:8]([O:7][CH3:6])[C:13]([O:14][CH3:15])=[C:12]([O:16][CH3:17])[CH:11]=4)=[O:23])[N:25]=3)=[CH:37][CH:36]=2)[CH:32]=[CH:33]1

참가 물질

7

반응물 3

HCID 758855-Bromo-1,2,3-trimethoxybenzeneHCID 53363879(R)-N-methoxy-N-methyl-2-(1-(phenylsulfonyl)-1H-indol-5-yl)-4,5-dihydrothiazole-4-carboxamideHCID 178418339Butyllithium

생성물 1

HCID 53361716(2-(1H-indol-5-yl)thiazol-4-yl)(3,4,5-trimethoxyphenyl)methanone

시약·촉매·용매 3

HCID 702Ethanol용매HCID 8028Tetrahydrofuran용매3회HCID 14798Sodium Hydroxide용매

실험 절차

To a solution of n-BuLi (1.6 M, 1.7 mL) in 8 mL THF was added a solution of 3,4,5-trimethoxybromobenzene (2.47 mmol) in 3 mL THF under −78° C. The mixture was allowed to stir for 2 h and a solution of Weinreb amide 65a (1.24 mmol) in 3 mL THF was charged. The temperature was allowed to increase at RT and stirred overnight. The reaction mixture was quenched with satd. NH4Cl, extracted with ethyl ether, dried with MgSO4. The solvent was removed under reduced pressure to yield a crude product, which was refluxed in 1 N NaOH in 5 mL ethanol solution to obtain the deprotected compound 31 and purified by column chromatography to obtain pure compound as a light yellow solid (36.3%). 1H NMR (300 MHz, CDCl3) δ 8.36 (br, s, 1H), 8.31 (s, 1H), 8.21 (s, 1H), 7.92, 7.89 (dd, 1H, J=1.8, 2.7 Hz), 7.46 (d, 1H,) 7.62 (s, 2H, J=8.7 Hz), 7.29 (t, 1H, J=2.7 Hz), 6.64 (br, 1H), 3.97 (s, 6H), 3.97 (s, 3H); MS (ESI) m/z 417.1 (M+Na)+, 392.9 (M−H)−.

후처리

  1. stirringstirred overnight
  2. customThe reaction mixture was quenched with satd
  3. extractionNH4Cl, extracted with ethyl ether
  4. dry with materialdried with MgSO4
  5. customThe solvent was removed under reduced pressure
  6. customto yield a crude product, which

출처 및 근거

ORD 기록
ord-00b200055c634dff82b6da8564206796
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09029408B2

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