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

HRID 2242963ノート

反応式

HRID 2242963 の反応式
[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]

参加物

4

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

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]+.

後処理

  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

出典と根拠

ORDレコード
ord-813307e5e34e4abe988a0e703607cec5
出典データセット
uspto-grants-2010_03
特許番号
US07674804B2

反応ノート

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