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

HRID 2376923Notes

Reaction equation

HRID 2376923 reaction equation
[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([NH: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]([NH: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 21949356N1-Methyl-5-(2-amino-5-cyano-4-pyridyl)amino-1H-1-indolecarboxamide

Product 1

HCID 21949381N1-Methyl-5-(2-((4-(pyrrolidin-1-yl)piperidin-1-yl)carbonyl)amino-5-cyano-4-pyridyl)amino-1H-1-indolecarboxamideYield 83.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

N1-Methyl-5-(2-amino-5-cyano-4-pyridyl)amino-1H-1-indolecarboxamide (50 mg, 0.16 mmol) was suspended in tetrahydrofuran (1 ml) at room temperature; triethylamine (0.057 ml, 0.41 mmol) and phenyl chloroformate (0.041 ml, 0.325 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 (100 mg, 0.648 mmol) was added to the residue; 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) to yield the title compound (65 mg, 0.134 mmol).

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)

Sources & evidence

ORD record
ord-e64ef5a28fbe4d0cae11f15b6fff7928
Source dataset
uspto-grants-2008_12
Patent number
US07468380B2

Reaction notes

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