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

HRID 572462Notes

Reaction equation

HRID 572462 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 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)−.

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-00b200055c634dff82b6da8564206796
Source dataset
uspto-grants-2015_05
Patent number
US09029408B2

Reaction notes

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