Ethanolamine → 1-[4-(3-cyano-1-cyclobutyl-6-ethoxy-1H-indol-2-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea

HRID 502263Notes

Reaction equation

HRID 502263 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](OC1C=CC([N+]([O-])=O)=CC=1)=[O:28].N1C=CC=CC=1.[CH2:45]([CH2:47][NH2:48])[OH:46]>C(Cl)Cl>[C:17]([C:16]1[C:15]2[C:10](=[CH:11][C:12]([O:19][CH2:20][CH3:21])=[CH:13][CH:14]=2)[N:9]([CH:22]2[CH2:23][CH2:24][CH2:25]2)[C:8]=1[C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:27]([NH:48][CH2:47][CH2:45][OH:46])=[O:28])=[CH:7][CH:6]=1)#[N:18]

Participants

6

Reactant 4

HCID 700EthanolamineHCID 1049PyridineHCID 821294-Nitrophenyl chloroformateHCID 250520112-(4-Aminophenyl)-1-cyclobutyl-6-ethoxy-indole-3-carbonitrile

Product 1

HCID 594256701-[4-(3-cyano-1-cyclobutyl-6-ethoxy-1H-indol-2-yl)-phenyl]-3-(2-hydroxy-ethyl)-ureaYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-(4-Aminophenyl)-1-cyclobutyl-6-ethoxy-1H-indole-3-carbonitrile (40 mg, 0.12 mmol), prepared as in example 1CM, step B, is combined with 4-nitrophenyl chloroformate (60 mg, 0.30 mmol), CH2Cl2 (400 μL), and pyridine (25 μL, 0.31 mmol). This suspension is stirred at room temperature for 1 hour. Ethanolamine (42 μL, 0.70 mmol) is added. After stirring at room temperature for an additional 30 min, the reaction mixture is diluted in CH2Cl2 and is washed with dilute aqueous NaOH to remove the yellow nitrophenol by-product. The organic layer is dried and concentrated. Purification by silica gel chromatography (CH2Cl2/Acetone, 7/3) yields 1-[4-(3-cyano-1-cyclobutyl-6-ethoxy-1H-indol-2-yl)-phenyl]-3-(2-hydroxy-ethyl)-urea (40 mg, 80%) as a white solid.

Workup

  1. stirringAfter stirring at room temperature for an additional 30 min
  2. washis washed with dilute aqueous NaOH
  3. customto remove the yellow nitrophenol by-product
  4. customThe organic layer is dried
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (CH2Cl2/Acetone, 7/3)

Sources & evidence

ORD record
ord-f0a3e3e986e64df2a5a83d8f4e0ba490
Source dataset
uspto-grants-2010_08
Patent number
US07772271B2

Reaction notes

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