Pyridine → 1-cyclopropylethyl N-[4-(3-cyano-1-cyclobutyl-6-ethoxy-indol-2-yl)phenyl]carbamate

HRID 506118Notes

Reaction equation

HRID 506118 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]([CH:22]3[CH2:25][CH2:24][CH2:23]3)[C:10]3[C:15]([C:16]=2[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][CH2:20][CH3:21])[CH:11]=3)=[CH:4][CH:3]=1.Cl[C:27]([O:29][C:30]1[CH:35]=[CH:34][C:33]([N+]([O-])=O)=C[CH:31]=1)=[O:28].N1C=CC=CC=1.C1(C(C)O)CC1>C(Cl)Cl.ClCCCl>[CH:35]1([CH:30]([O:29][C:27](=[O:28])[NH:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[N:9]([CH:22]4[CH2:23][CH2:24][CH2:25]4)[C:10]4[C:15]([C:16]=3[C:17]#[N:18])=[CH:14][CH:13]=[C:12]([O:19][CH2:20][CH3:21])[CH:11]=4)=[CH:6][CH:7]=2)[CH3:31])[CH2:34][CH2:33]1

Participants

7

Reactant 4

HCID 1049PyridineHCID 791041-CyclopropylethanolHCID 821294-Nitrophenyl chloroformateHCID 250520112-(4-Aminophenyl)-1-cyclobutyl-6-ethoxy-indole-3-carbonitrile

Product 1

HCID 497722241-cyclopropylethyl N-[4-(3-cyano-1-cyclobutyl-6-ethoxy-indol-2-yl)phenyl]carbamateYield 60.1%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

2-(4-Aminophenyl)-1-cyclobutyl-6-ethoxy-1H-indole-3-carbonitrile (50 mg, 0.15 mmol), prepared as in example 1CM, step B, is combined with 4-nitrophenyl chloroformate (76 mg, 0.38 mmol), DCE (0.5 mL), and pyridine (30 μL, 0.37 mmol). This suspension is stirred at room temperature for 1 h. Rac-cyclopropyl methyl carbinol (100 μL, 0.98 mmol) is added. This mixture is heated at 75° C. overnight. The reaction mixture is then diluted in CH2Cl2 and is washed with dilute aqueous NaOH to remove the yellow nitrophenol byproduct. The organic layer is dried and concentrated. Purification by silica gel chromatography (CH2Cl2) yields rac-[4-(3-cyano-1-cyclobutyl-6-ethoxy-1H-indol-2-yl)-phenyl]-carbamic acid 1-cyclopropyl-ethyl ester (40 mg, 60%) as a white solid.

Workup

  1. temperatureThis mixture is heated at 75° C. overnight
  2. washis washed with dilute aqueous NaOH
  3. customto remove the yellow nitrophenol byproduct
  4. customThe organic layer is dried
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (CH2Cl2)

Sources & evidence

ORD record
ord-8b30daa730ba4553a78af4dd76907b5f
Source dataset
uspto-grants-2010_08
Patent number
US07781478B2

Reaction notes

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