Triethylamine → 1-methyl-1H-indole-3-carboxylic acid (5-bromo-6-methoxy-naphthalen-2-ylmethyl)-methyl-amide

HRID 1357275Notes

Reaction equation

HRID 1357275 reaction equation
[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:11](Cl)=[O:12])=[CH:3]1.[Br:14][C:15]1[C:24]([O:25][CH3:26])=[CH:23][CH:22]=[C:21]2[C:16]=1[CH:17]=[CH:18][C:19]([CH2:27][N-:28][CH3:29])=[CH:20]2.C(N(CC)CC)C>C(Cl)Cl>[Br:14][C:15]1[C:24]([O:25][CH3:26])=[CH:23][CH:22]=[C:21]2[C:16]=1[CH:17]=[CH:18][C:19]([CH2:27][N:28]([CH3:29])[C:11]([C:4]1[C:5]3[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=3)[N:2]([CH3:1])[CH:3]=1)=[O:12])=[CH:20]2

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 151324411-Methyl-1H-indole-3-carbonyl chlorideHCID 86587392(5-Bromo-6-methoxy-naphthalen-2-ylmethyl)-methyl-amide

Product 1

HCID 865873911-methyl-1H-indole-3-carboxylic acid (5-bromo-6-methoxy-naphthalen-2-ylmethyl)-methyl-amideYield 79.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of 1-methyl-1H-indole-3-carbonyl chloride (27 mmol), prepared in the previous step, in 50 mL of methylene chloride was added dropwise under nitrogen over 1.5 h to a solution of (5-bromo-6-methoxy-naphthalen-2-ylmethyl)-methyl-amide (7.56 g, 27 mmol), prepared in step 7 of Example 36, and triethylamine (3.76 mL, 27 mmol) in 200 mL of methylene chloride at room temperature. The solution was stirred at room temperature for 22 h (overnight). The reaction was extracted with 1N HCl. The aqueous layer was separated and extracted two additional times with methylene chloride. The organic extracts were combined, dried (MgSO4) and the solvent removed under reduced pressure to give 11.52 g of an off white solid. The solid was recrystallized from methylene chloride-isopropanol. Off-white crystals were collected by filtration and dried under reduced pressure to give 1-methyl-1H-indole-3-carboxylic acid (5-bromo-6-methoxy-naphthalen-2-ylmethyl)-methyl-amide (9.3389 g, 79%) as an off white solid, mp 168-169° C.

Workup

  1. extractionThe reaction was extracted with 1N HCl
  2. customThe aqueous layer was separated
  3. extractionextracted two additional times with methylene chloride
  4. dry with materialdried (MgSO4)
  5. customthe solvent removed under reduced pressure
  6. customto give 11.52 g of an off white solid
  7. customThe solid was recrystallized from methylene chloride-isopropanol
  8. filtrationOff-white crystals were collected by filtration
  9. customdried under reduced pressure

Sources & evidence

ORD record
ord-413cf4ff102e46bbbfc7ce9ae512e91d
Source dataset
uspto-grants-2003_07
Patent number
US06589970B2

Reaction notes

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