Diisopropylethylamine → HCID 11180570, compound

HRID 2118115Notes

Reaction equation

HRID 2118115 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]([C:18]([O:20]CC)=[O:19])=[C:5]2[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(C(C)C)CC)(C)C.[F:38][C:39]([F:52])([F:51])[O:40][C:41]1[CH:46]=[CH:45][C:44]([S:47](Cl)(=[O:49])=[O:48])=[CH:43][CH:42]=1.O.[OH-].[Li+]>C(Cl)Cl>[CH2:11]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([NH:1][S:47]([C:44]3[CH:43]=[CH:42][C:41]([O:40][C:39]([F:38])([F:51])[F:52])=[CH:46][CH:45]=3)(=[O:49])=[O:48])=[CH:10][CH:9]=2)[C:5]([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)=[C:6]1[C:18]([OH:20])=[O:19])[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 168937Lithium hydroxide, monohydrateHCID 523102p-(Trifluoromethoxy)benzenesulphonyl chlorideHCID 69229300ethyl 5-amino-1-benzyl-3-phenyl-1H-indole-2-carboxylate

Product 1

HCID 11180570HCID 11180570, compoundYield 56.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Ethyl 5-amino-1-benzyl-3-phenyl-1H-indole-2-carboxylate (0.23 g, 0.67 mmol) was dissolved in 7 mL of methylene chloride. To the solution was added diisopropylethylamine (0.5 mL, 2.9 mmol) and 4-trifluoromethoxy-benzenesulfonyl chloride (0.13 g, 0.5 mmol). After being stirred at room temperature overnight the reaction was concentrated and the residue was re-dissolved in 10 mL of 2:1:1 THF/MeOH/water. Lithium hydroxide monohydrate (0.15 g, 3.6 mmol) was added and the mixture was stirred at 40° C. overnight. Most of the organic solvents was removed and the reaction mixture was made acidic (pH 6) with glacial acetic acid, and the solid was collected and purified by semi-preparative HPLC (Column: Phenomenex C18 Luna 21.6 mm×60 mm, 5 μM; Solvent A: Water (0.1% TFA buffer); Solvent B: Acetonitrile (0.1% TFA buffer); Solvent Gradient: Time 0: 0% B; 10 min: 100% B; Hold 100% B 5 min. Flow Rate: 22.5 mL/min). The product was collected based on UV absorption and concentrated to give the title compound as a pale yellow solid (0.16 g, 45%):

Workup

  1. concentrationwas concentrated
  2. dissolutionthe residue was re-dissolved in 10 mL of 2:1:1 THF/MeOH/water
  3. stirringthe mixture was stirred at 40° C. overnight
  4. customMost of the organic solvents was removed
  5. customthe solid was collected
  6. custompurified by semi-preparative HPLC (Column: Phenomenex C18 Luna 21.6 mm×60 mm, 5 μM; Solvent A: Water (0.1% TFA buffer); Solvent B: Acetonitrile (0.1% TFA buffer); Solvent Gradient: Time 0: 0% B; 10 min: 100% B; Hold 100% B 5 min. Flow Rate: 22.5 mL/min)
  7. customThe product was collected
  8. custombased on UV absorption
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-a06aa89162114f5d88ecc55c832ab3d4
Source dataset
uspto-grants-2008_10
Patent number
US07442805B2

Reaction notes

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