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

HRID 723452노트

반응식

HRID 723452 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매2회

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온도
0 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-f523665773b84112866fa2adb6e55671
출처 데이터셋
uspto-grants-2006_11
특허 번호
US07141571B2

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