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

HRID 1009648Notes

Reaction equation

HRID 1009648 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, ias 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-ffdb24948618411c9c44d3c4a331518d
Source dataset
uspto-grants-2011_07
Patent number
US07973069B2

Reaction notes

Loading…