2,4-Dichloropyrimidine → tert-Butyl 4-((2-chloropyrimidin-4-yl)amino)piperidine-1-carboxylate

HRID 2242963노트

반응식

HRID 2242963 반응식
[Cl:1][C:2]1[N:7]=[C:6](Cl)[CH:5]=[CH:4][N:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([NH2:22])[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10]>CN(C=O)C>[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([NH:22][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([Cl:1])[N:7]=2)[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:10])[CH3:11]

참가 물질

4

반응물 2

HCID 775312,4-DichloropyrimidineHCID 12682914-Amino-1-Boc-piperidine

생성물 1

HCID 22309647tert-Butyl 4-((2-chloropyrimidin-4-yl)amino)piperidine-1-carboxylate

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A mixture of 2,4-dichloro-pyrimidine (4.0 g, 26.85 mmol, 1.0 equiv; commercially available) and 4-amino-piperidine-1-carboxylic acid tert-butyl ester (6.45 g, 32.22 mmol, 1.2 equiv) in anhydrous DMF (100 mL) was stirred at rt for 18 h. The organic phase was concentrated under reduced pressure and the crude reaction mixture purified with silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate providing 3.2 g (38%) of the title compound. 1H NMR (400 MHz, CDCl3): δ1.35-1.45 (m, 2H), 1.47 (s, 9H), 1.99-2.03 (m, 2H), 2.91-2.97 (m, 2H), 3.81-3.90 (m, 1H), 4.04-4.07 (br d, 2H), 5.33 (d, J=8.0 Hz, 1H), 6.25 (d, J=4.0 Hz, 1H), 7.98 (d, J=4.0 Hz, 1H). 13C NMR (75 MHz, DMSO): δ 28.05, 30.94, 42.04, 46.69, 78.64, 105.13, 153.86, 155.57, 159.81, 162.72. MS (ISP): 313.1 [M+H]+.

후처리

  1. concentrationThe organic phase was concentrated under reduced pressure
  2. customthe crude reaction mixture
  3. custompurified with silica column chromatography
  4. washeluting with a gradient of heptane/ethyl acetate providing 3.2 g (38%) of the title compound

출처 및 근거

ORD 기록
ord-813307e5e34e4abe988a0e703607cec5
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07674804B2

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