Diisopropylethylamine → tert-butyl (3S)-3-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]piperidine-1-carboxylate

HRID 74870

반응식

HRID 74870 반응식
[NH2:1][C@H:2]1[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]1.[Cl:15][C:16]1[N:21]=[C:20](Cl)[C:19]([F:23])=[CH:18][N:17]=1.C(N(C(C)C)CC)(C)C>C(O)(C)C>[Cl:15][C:16]1[N:21]=[C:20]([NH:1][C@H:2]2[CH2:7][CH2:6][CH2:5][N:4]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:3]2)[C:19]([F:23])=[CH:18][N:17]=1

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 1501975tert-butyl (3S)-3-aminopiperidine-1-carboxylate

생성물 1

HCID 75412621tert-butyl (3S)-3-[(2-chloro-5-fluoro-pyrimidin-4-yl)amino]piperidine-1-carboxylate

시약·촉매·용매 1

HCID 3776Isopropanol용매

반응 조건

온도
80 °C

실험 절차

To a solution of tert-butyl (3S)-3-aminopiperidine-1-carboxylate (8.1 g, 40.4 mmol) and 2,4-dichloro-5-fluoro-pyrimidine (6.6 g, 39.8 mmol) in isopropanol (80 mL) was added N,N-diisopropyl-N-ethylamine (9.0 mL, 51.7 mmol). The reaction mixture was warmed to 80° C. and stirred for 17 hours. All volatiles were removed at reduced pressure and the residue was dissolved in EtOAc. The organic layer was partitioned with water and the layers were separated. The organic phase was washed with brine, dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was dissolved in CH2Cl2 and purified by silica gel chromatography (0-50% EtOAc/Hexanes) to afford the desired product, 5a.

후처리

  1. customAll volatiles were removed at reduced pressure
  2. dissolutionthe residue was dissolved in EtOAc
  3. customThe organic layer was partitioned with water
  4. customthe layers were separated
  5. washThe organic phase was washed with brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. dissolutionThe resulting residue was dissolved in CH2Cl2
  10. custompurified by silica gel chromatography (0-50% EtOAc/Hexanes)

출처 및 근거

ORD 기록
ord-910471e5d46f4d8b857cb7c1c32da199
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08829007B2

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