Acetic Acid → 3-(2-tert-butylphenyl)-N-p-tolyl-1H-indole-1-carboxamide

HRID 2423219Notes

Reaction equation

HRID 2423219 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[N:30]([C:33]1[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=1)=[C:31]=[O:32].C(O)(=O)C>O1CCCC1.CO>[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[N:13]([C:31]([NH:30][C:33]2[CH:38]=[CH:37][C:36]([CH3:39])=[CH:35][CH:34]=2)=[O:32])[CH:12]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 693254-Methylphenyl isocyanateHCID 2724254Sodium bis(trimethylsilyl)amideHCID 672410893-(2-tert-butylphenyl)-1H-indole

Product 1

HCID 598045193-(2-tert-butylphenyl)-N-p-tolyl-1H-indole-1-carboxamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

3-(2-tert-Butylphenyl)-1H-indole (24.1 mg, 0.0967 mmol) in 0.5 mL anhydrous tetrahydrofuran was treated with 1M NaN(TMS)2 in THF (0.2 mL) and stirred for 5 minutes at ambient temperature. 1-Isocyanato-4-methylbenzene (15 μL, 0.116 mmol) in 0.5 mL anhydrous tetrahydrofuran was added and stirred for 5 minutes at ambient temperature. 50 μL acetic acid and 200 μL methanol are added and the reaction mixture charged to a silica gel column and purified by eluting with a gradient of ethyl acetate and hexanes to give 3-(2-tert-butylphenyl)-N-p-tolyl-1H-indole-1-carboxamide which was further purified by reverse phase HPLC to give Example 49 (19.1 mg, 52%) as a colorless solid and 99.5% purity. LC/MS (ESI+) 383.4.

Workup

  1. stirringstirred for 5 minutes at ambient temperature
  2. additionthe reaction mixture charged to a silica gel column
  3. custompurified
  4. washby eluting with a gradient of ethyl acetate and hexanes

Sources & evidence

ORD record
ord-18194329355d4315a01136192dcbec83
Source dataset
uspto-grants-2011_06
Patent number
US07960569B2

Reaction notes

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