Water → N1-Methyl-5-(2-(pyrrolidin-1-ylcarbonyl)amino-5-cyano-4-pyridyl)oxy-1H-1-indolecarboxamide

HRID 2376921Notes

Reaction equation

HRID 2376921 reaction equation
[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[C:20]([C:21]#[N:22])=[CH:19][N:18]=[C:17]([NH2:23])[CH:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4].[CH2:24]([N:26]([CH2:29][CH3:30])[CH2:27]C)[CH3:25].ClC(OC1C=CC=CC=1)=[O:33].O>O1CCCC1>[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][C:15]3[C:20]([C:21]#[N:22])=[CH:19][N:18]=[C:17]([NH:23][C:27]([N:26]4[CH2:29][CH2:30][CH2:25][CH2:24]4)=[O:33])[CH:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 21949164N1-methyl-5-(2-amino-5-cyano-4-pyridyl)oxy-1H-1-indolecarboxamide

Product 1

HCID 21949308N1-Methyl-5-(2-(pyrrolidin-1-ylcarbonyl)amino-5-cyano-4-pyridyl)oxy-1H-1-indolecarboxamideYield 22.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N1-Methyl-5-(2-amino-5-cyano-4-pyridyl)oxy-1H-1-indolecarboxamide (20 mg) synthesized in Example 215 was suspended in tetrahydrofuran (0.5 ml) at room temperature; triethylamine (0.121 ml, 0.868 mmol) and phenyl chloroformate (0.08 ml, 0.633 mmol) was added thereto while stirring; and the reaction mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture; this was subjected to extraction with ethyl acetate, washed with brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. N,N-Dimethylformamide and pyrrolidine (0.013 ml) was added to a portion of the residue (14 mg); and the reaction mixture was stirred overnight. The reaction mixture was partitioned between ethyl acetate and water; and the organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol). The resultant was washed with a solvent mixture (ether:hexane=1:1) to yield the title compound as crystals (6 mg).

Workup

  1. stirringand the reaction mixture was stirred at room temperature for 2 hours
  2. extractionthis was subjected to extraction with ethyl acetate
  3. washwashed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. additionN,N-Dimethylformamide and pyrrolidine (0.013 ml) was added to a portion of the residue (14 mg)
  7. stirringand the reaction mixture was stirred overnight
  8. customThe reaction mixture was partitioned between ethyl acetate and water
  9. dry with materialand the organic layer was dried over anhydrous sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol)
  12. washThe resultant was washed with a solvent mixture (ether:hexane=1:1)

Sources & evidence

ORD record
ord-fd0fc016f15f41e698d72915dd06f4db
Source dataset
uspto-grants-2008_12
Patent number
US07468380B2

Reaction notes

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