Toluene → 4-(5-chloro-3-methyl-2-pyridin-3-yl-1H-indol-1-ylmethyl)-benzoic acid methyl ester

HRID 593498Notes

Reaction equation

HRID 593498 reaction equation
Cl.[Cl:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)=[C:6]2[CH3:18].C[Si]([N-][Si](C)(C)C)(C)C.[K+].C1(C)C=CC=CC=1.[CH3:36][O:37][C:38](=[O:47])[C:39]1[CH:44]=[CH:43][C:42]([CH2:45]Br)=[CH:41][CH:40]=1>C1COCC1.CO>[CH3:36][O:37][C:38](=[O:47])[C:39]1[CH:44]=[CH:43][C:42]([CH2:45][N:8]2[C:9]3[C:5](=[CH:4][C:3]([Cl:2])=[CH:11][CH:10]=3)[C:6]([CH3:18])=[C:7]2[C:12]2[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=2)=[CH:41][CH:40]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 256687Methyl 4-(bromomethyl)benzoateHCID 3251421Potassium bis(trimethylsilyl)amideHCID 445539625-chloro-3-methyl-2-pyridin-3-yl-1H-indole hydrochloride

Product 1

HCID 445541384-(5-chloro-3-methyl-2-pyridin-3-yl-1H-indol-1-ylmethyl)-benzoic acid methyl ester

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-chloro-3-methyl-2-pyridin-3-yl-1H-indole hydrochloride (Example 2, 558 mg, 2.0 mmol) in THF (20 mL) is added 0.5 M KHMDS in toluene (8.8 mL, 4.4 mmol) and the mixture is stirred at room temperature for 30 min, whereupon 4-bromomethyl-benzoic acid methyl ester (916 mg, 4.0 mmol). The reaction mixture is stirred for 3 h. Methanol is added to quench the reaction and the solvents are removed in vacuo. The residue is purified by flash chromatography with 1-3% methanol in dichloromethane to give 4-(5-chloro-3-methyl-2-pyridin-3-yl-1H-indol-1-ylmethyl)-benzoic acid methyl ester. MS (ESI) m/z 391.3 and 393.3 (M+H)+.

Workup

  1. customto quench
  2. customthe reaction
  3. customthe solvents are removed in vacuo
  4. customThe residue is purified by flash chromatography with 1-3% methanol in dichloromethane

Sources & evidence

ORD record
ord-4a9668ad391142568b2835616aa970a7
Source dataset
uspto-grants-2016_01
Patent number
US09242963B2

Reaction notes

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