4-Aminopyridine → 5-[(4-Amino-1-piperidinyl)methyl]-N-4-pyridinylpyrrolo[2,1-f][1,2,4]triazin-4-amine

HRID 723452Notes

Reaction equation

HRID 723452 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([NH2:7])=[CH:3][CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[Br-].Cl[C:20]1[C:25]2=[C:26]([CH2:29][N+](CC)(CC)CC)[CH:27]=[CH:28][N:24]2[N:23]=[CH:22][N:21]=1.C(OC(=O)[NH:43][CH:44]1[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]1)(C)(C)C>C1COCC1.CN(C=O)C>[NH2:7][CH:4]1[CH2:5][CH2:6][N:1]([CH2:29][C:26]2[CH:27]=[CH:28][N:24]3[C:25]=2[C:20]([NH:43][C:44]2[CH:49]=[CH:48][N:47]=[CH:46][CH:45]=2)=[N:21][CH:22]=[N:23]3)[CH2:2][CH2:3]1

Participants

7

Reactant 4

HCID 17274-AminopyridineHCID 7238334-(N-Boc-amino)piperidineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 11544775(4-Chloro-pyrrolo[2,1-f][1,2,4]triazin-5-ylmethyl)-triethyl-ammonium bromide

Product 1

HCID 116239805-[(4-Amino-1-piperidinyl)methyl]-N-4-pyridinylpyrrolo[2,1-f][1,2,4]triazin-4-amineYield 53%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a mixture of pyridin-4-ylamine (34 mg, 0.361 mmol) in THF (500 μl) was added 1N NaHMDS in THF (722 μl, 0.722 mmol). The mixture was cooled to 0° C. and a suspension of 1D (125 mg, 0.27 mmol) in DMF (800 μl) was added. The mixture was stirred at this temperature for 0.5 h. and piperidin-4-yl-carbamic acid tert-butyl ester (144 mg, 0.72 mmol)-was added to the cold mixture. The reaction mixture was heated to 50° C. for 10 min and concentrated to remove THF. TFA (1 ml) was added, the mixture was stirred until the protecting group was removed (2 h) (progress was monitored by HPLC). TFA was removed in vacuo and saturated NaHCO3 was added. The mixture was extracted with EtOAc and the combined extracts were dried, concentrated and triturated first with Et2O to give the title compound (46 mg, 53%). Analytical HPLC retention time=0.51 min (Chromolith SpeedROD 4.6×50 mm, 10–90% aqueous methanol over 4 minutes containing 0.1% TFA, 4 ml/min, monitoring at 220 nm) and a LC/MS M++1=324.

Workup

  1. additionwas added
  2. temperatureThe reaction mixture was heated to 50° C. for 10 min
  3. concentrationconcentrated
  4. customto remove THF
  5. additionTFA (1 ml) was added
  6. stirringthe mixture was stirred until the protecting group
  7. customwas removed (2 h) (progress was monitored by HPLC)
  8. customTFA was removed in vacuo and saturated NaHCO3
  9. additionwas added
  10. extractionThe mixture was extracted with EtOAc
  11. customthe combined extracts were dried
  12. concentrationconcentrated
  13. customtriturated first with Et2O

Sources & evidence

ORD record
ord-f523665773b84112866fa2adb6e55671
Source dataset
uspto-grants-2006_11
Patent number
US07141571B2

Reaction notes

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