Triethylamine → N1-Methyl-5-(2-((4-(pyrrolidin-1-yl)piperidin-1-yl)carbonyl)amino-5-cyano-4-pyridyl)oxy-1H-1-indolecarboxamide

HRID 2215597Notes

Reaction equation

HRID 2215597 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].C(N(CC)CC)C.Cl[C:32](OC1C=CC=CC=1)=[O:33].[N:41]1([CH:46]2[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]2)[CH2:45][CH2:44][CH2:43][CH2:42]1>O1CCCC1.CN(C)C=O.O>[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:32]([N:49]4[CH2:50][CH2:51][CH:46]([N:41]5[CH2:45][CH2:44][CH2:43][CH2:42]5)[CH2:47][CH2:48]4)=[O:33])[CH:16]=3)=[CH:11][CH:12]=2)[CH:7]=[CH:6]1)=[O:4]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 15891Phenyl chloroformateHCID 787034-(1-Pyrrolidinyl)piperidineHCID 21949164N1-methyl-5-(2-amino-5-cyano-4-pyridyl)oxy-1H-1-indolecarboxamide

Product 1

HCID 21949191N1-Methyl-5-(2-((4-(pyrrolidin-1-yl)piperidin-1-yl)carbonyl)amino-5-cyano-4-pyridyl)oxy-1H-1-indolecarboxamideYield 25.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

N1-Methyl-5-(2-amino-5-cyano-4-pyridyl)oxy-1H-1-indolecarboxamide (15 mg, 0.049 mmol) synthesized in Example 215 was suspended in tetrahydrofuran (0.5 ml) at room temperature; triethylamine (17 μl, 0.122 mmol) and phenyl chloroformate (14 μl, 0.072 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 (0.5 ml) and 4-(1-pyrrolidinyl)piperidine (28 mg, 0.18 mmol) was added to a portion of the residue (14 mg); and the reaction mixture was stirred at room temperature overnight. The reaction mixture was partitioned between ethyl acetate and water; and the organic layer was dried over anhydrous sodium sulfate. This was concentrated under reduced pressure; and 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); and the solid was filtered off 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. stirringand the reaction mixture was stirred at room temperature overnight
  7. customThe reaction mixture was partitioned between ethyl acetate and water
  8. dry with materialand the organic layer was dried over anhydrous sodium sulfate
  9. concentrationThis was concentrated under reduced pressure
  10. customand the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate-methanol)
  11. washThe resultant was washed with a solvent mixture (ether: hexane=1:1)
  12. filtrationand the solid was filtered off

Sources & evidence

ORD record
ord-c439004c443a448b9867b336846af145
Source dataset
uspto-grants-2006_09
Patent number
US07109219B2

Reaction notes

Loading…