2-Chloroethyl isocyanate → N1-Cyclopropyl-5-((2-(((2-chloroethylamino)carbonyl)amino)-4-pyridyl)oxy)-1H-1-indolecarboxamide

HRID 2376930Notes

Reaction equation

HRID 2376930 reaction equation
[CH:1]1([NH:4][C:5]([N:7]2[C:15]3[C:10](=[CH:11][C:12]([O:16][C:17]4[CH:22]=[CH:21][N:20]=[C:19]([NH2:23])[CH:18]=4)=[CH:13][CH:14]=3)[CH:9]=[CH:8]2)=[O:6])[CH2:3][CH2:2]1.[Cl:24][CH2:25][CH2:26][N:27]=[C:28]=[O:29]>O1CCCC1>[CH:1]1([NH:4][C:5]([N:7]2[C:15]3[C:10](=[CH:11][C:12]([O:16][C:17]4[CH:22]=[CH:21][N:20]=[C:19]([NH:23][C:28]([NH:27][CH2:26][CH2:25][Cl:24])=[O:29])[CH:18]=4)=[CH:13][CH:14]=3)[CH:9]=[CH:8]2)=[O:6])[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 160352-Chloroethyl isocyanateHCID 21949236N1-cyclopropyl-5-((2-amino-4-pyridyl)oxy)-1H-1-indolecarboxamide

Product 1

HCID 21949416N1-Cyclopropyl-5-((2-(((2-chloroethylamino)carbonyl)amino)-4-pyridyl)oxy)-1H-1-indolecarboxamideYield 52.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

N1-cyclopropyl-5-((2-amino-4-pyridyl)oxy)-1H-1-indolecarboxamide (400 mg, CAS No. 417722-12-4) described in WO02/32872, 2-chloroethyl isocyanate (150 mg) and tetrahydrofuran (5 ml) were stirred at 80° C. for 1.5 hours. The mixture was cooled to room temperature, silica gel was added, and the solvent was distilled off under reduced pressure. The silica gel was charged into a dry column packed with silica gel, and purification was performed by column chromatography (hexane:ethyl acetate=1:1, followed by ethyl acetate) to yield 280 mg of a colorless powder.

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. additionsilica gel was added
  3. distillationthe solvent was distilled off under reduced pressure
  4. additionThe silica gel was charged into a dry column
  5. custompacked with silica gel, and purification

Sources & evidence

ORD record
ord-898987b107d14825a2551d5e46eedf1e
Source dataset
uspto-grants-2008_12
Patent number
US07468380B2

Reaction notes

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