2,4,5,6-Tetrachloropyrimidine → 4-(2,5,6-Trichloro-pyrimidin-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

HRID 2242984

반응식

HRID 2242984 반응식
[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([Cl:9])=[C:4]([Cl:10])[N:3]=1.[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([NH2:24])[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].C(N(C(C)C)C(C)C)C>C(#N)C>[C:11]([O:15][C:16]([N:18]1[CH2:23][CH2:22][CH:21]([NH:24][C:6]2[C:5]([Cl:9])=[C:4]([Cl:10])[N:3]=[C:2]([Cl:1])[N:7]=2)[CH2:20][CH2:19]1)=[O:17])([CH3:14])([CH3:12])[CH3:13]

참가 물질

5

반응물 3

HCID 156902,4,5,6-TetrachloropyrimidineHCID 81531DiisopropylethylamineHCID 12682914-Amino-1-Boc-piperidine

생성물 1

HCID 866185544-(2,5,6-Trichloro-pyrimidin-4-ylamino)-piperidine-1-carboxylic acid tert-butyl ester

시약·촉매·용매 1

HCID 6342Acetonitrile용매

실험 절차

A solution of 2,4,5,6-tetrachloro-pyrimidine (1.67 g, 7.68 mmol, 1.0 equiv; commercially available), 4-amino-piperidine-1-carboxylic acid tert-butyl ester (2.0 g, 10.0 mmol, 1.3 equiv) and N-ethyl diisopropylamine (3.0 mL, 2.3 g, 17.7 mmol, 2.3 equiv) in acetonitrile (16 mL) was heated by microwave irradiation to 160° C. for 20 min. The reaction mixture was concentrated under reduced pressure and the crude material purified by silica column chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of heptane/ethyl acetate providing 0.85 g (29%) of the title compound. 1H NMR (400 MHz, DMSO): δ 1.41 (s, 9H), 1.49-1.60 (m, 2H), 1.73-1.77 (m, 2H), 2.81 (br s, 2H), 3.95-3.98 (m, 2H), 4.09-4.16 (m, 1H), 7.88 (d, J=8.0 Hz, 1H). 13C NMR (100 MHz, DMSO): δ 28.07, 30.45, 43.33, 48.90, 78.65, 109.37, 153.80, 154.62, 155.66, 158.74. MS (ISP): 383.0 [M+H]+.

후처리

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customthe crude material purified by silica column chromatography
  3. washeluting with a gradient of heptane/ethyl acetate providing 0.85 g (29%) of the title compound

출처 및 근거

ORD 기록
ord-6cf7ea6f2905422480bfaeb32aa643c5
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07674804B2

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