Potassium Carbonate → tert-Butyl (1-pyridazin-3-ylpiperidin-4-yl)carbamate

HRID 1485579

반응식

HRID 1485579 반응식
[NH:1]1[CH2:6][CH2:5][CH:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:3][CH2:2]1.Br[C:16]1[N:17]=[N:18][CH:19]=[CH:20][CH:21]=1.[F-].[Cs+].C([O-])([O-])=O.[K+].[K+]>CS(C)=O.C(Cl)Cl.O>[N:17]1[CH:16]=[CH:21][CH:20]=[C:19]([N:1]2[CH2:2][CH2:3][CH:4]([NH:7][C:8](=[O:14])[O:9][C:10]([CH3:11])([CH3:13])[CH3:12])[CH2:5][CH2:6]2)[N:18]=1

참가 물질

8

반응물 4

HCID 11430Potassium CarbonateHCID 25953Cesium fluorideHCID 7238334-(N-Boc-amino)piperidineHCID 131266993-Bromopyridazine

생성물 1

HCID 86625871tert-Butyl (1-pyridazin-3-ylpiperidin-4-yl)carbamate수율 35.4%

시약·촉매·용매 3

HCID 679Dimethyl Sulfoxide용매HCID 962Water용매HCID 6344Dichloromethane용매

반응 조건

온도
100 °C

실험 절차

The reaction mixture of tert-butyl piperidin-4-ylcarbamate (250 mg, 1.25 mmol), 3-bromopyridazine (258 mg, 1.62 mmol), CsF (37.9 mg, 0.25 mmol), and K2CO3 (518 mg, 3.74 mmol) in DMSO (12.5 mL) was heated at 100° C. for 20 h. Water and DCM were poured into the mixture, and the separated aqueous layer was extracted with DCM, the combined organic layers were dried over Na2SO4, filtered, concentrated in vacuo. The residue was purified by column chromatography (Hexane:EtOAc=1:1) to give tert-butyl 1-(pyridazine-3-yl)piperidin-4-ylcarbamate (123 mg, 35%) as a pale yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 1.45 (9H, s), 1.92-2.12 (2H, m), 3.03-3.17 (2H, m), 3.55-3.80 (2H, m), 4.25-4.38 (2H, m), 4.52 (1H, brs), 6.92 (1H, d, J=9.2 Hz), 7.20 (1H, dd, J=4.4, 9.2 Hz), 8.56 (1H, d, J=4.4 Hz). NH peak was not observed. m/z=279.06 [M+1]+.

후처리

  1. extractionthe separated aqueous layer was extracted with DCM
  2. dry with materialthe combined organic layers were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by column chromatography (Hexane:EtOAc=1:1)

출처 및 근거

ORD 기록
ord-23525637b4f04fb6a18f2c15dd65498f
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09422298B2

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