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

HRID 522579Notes

Reaction equation

HRID 522579 reaction equation
[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

Participants

7

Reactant 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

Product 1

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

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent3×HCID 14798Sodium HydroxideSolvent

Procedure

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 66a and purified by column chromatography to obtain pure compound as a light yellow solid (36.3%). 1H NMR (300M, 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)−.

Workup

  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

Sources & evidence

ORD record
ord-4d0b0727a7c84cdf8376d7859e56cf44
Source dataset
uspto-grants-2016_05
Patent number
US09334242B2

Reaction notes

Loading…