Formaldehyde → 1,1-Dimethylethyl (2S)-2-methyl-4-{[4-methyl-6-(methylamino)-3-pyridinyl]methyl}-1-piperazinecarboxylate

HRID 644750노트

반응식

HRID 644750 반응식
[NH2:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][N:9]2[CH2:14][CH2:13][N:12]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[C@@H:11]([CH3:22])[CH2:10]2)=[C:4]([CH3:23])[CH:3]=1.[CH2:24]=O.C[O-].[Na+].[BH4-].[Na+]>CO>[CH3:22][C@H:11]1[CH2:10][N:9]([CH2:8][C:5]2[CH:6]=[N:7][C:2]([NH:1][CH3:24])=[CH:3][C:4]=2[CH3:23])[CH2:14][CH2:13][N:12]1[C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16]

참가 물질

6

반응물 4

HCID 712FormaldehydeHCID 4311764Sodium borohydrideHCID 10942334Sodium MethoxideHCID 592621751,1-Dimethylethyl (2S)-4-[(6-amino-4-methyl-3-pyridinyl)methyl]-2-methyl-1-piperazinecarboxylate

생성물 1

HCID 592621971,1-Dimethylethyl (2S)-2-methyl-4-{[4-methyl-6-(methylamino)-3-pyridinyl]methyl}-1-piperazinecarboxylate수율 52.7%

시약·촉매·용매 1

HCID 887Methanol용매

반응 조건

온도
50 °C

실험 절차

To 1,1-dimethylethyl (2S)-4-[(6-amino-4-methyl-3-pyridinyl)methyl]-2-methyl-1-piperazinecarboxylate (D100) (0.067 g, 0.21 mmol) in dry MeOH (4 mL) under an argon atmosphere was added paraformaldehyde (0.019 g, 0.63 mmol) and sodium methoxide (0.057 g, 1.00 mmol). The mixture was stirred at 50° C. overnight then sodium borohydride (0.024 g, 0.63 mmol) was added and the reaction stirred at 50° C. for 24 h. The reaction mixture was concentrated in vacuo. The residue was partitioned between DCM and saturated aqueous NaHCO3 and stirred for 0.5 h. The aqueous phase was extracted with DCM (3×5 mL) and the combined organics were dried and concentrated to give a crude colourless oil. Column chromatography eluting with 0-10% MeOH/DCM gave the crude title compound as a colourless oil (0.037 g) which was used in the next step without further purification. MS (ES): MH+ 335.3.

후처리

  1. stirringthe reaction stirred at 50° C. for 24 h
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. customThe residue was partitioned between DCM and saturated aqueous NaHCO3
  4. stirringstirred for 0.5 h
  5. extractionThe aqueous phase was extracted with DCM (3×5 mL)
  6. customthe combined organics were dried
  7. concentrationconcentrated
  8. customto give a crude colourless oil
  9. washColumn chromatography eluting with 0-10% MeOH/DCM

출처 및 근거

ORD 기록
ord-061f9e2932a04828bacc5573fe5e823a
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07700599B2

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