Diisopropylethylamine → 6-(((2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile

HRID 882217

반응식

HRID 882217 반응식
[NH2:1][C@H:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([Br:12])[CH:10]=2)[N:5]([C:13](=[O:15])[CH3:14])[C@@H:4]([CH3:16])[CH2:3]1.Cl[C:18]1[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][N:19]=1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1>[C:13]([N:5]1[C:6]2[C:11](=[CH:10][C:9]([Br:12])=[CH:8][CH:7]=2)[C@H:2]([NH:1][C:18]2[CH:25]=[CH:24][C:21]([C:22]#[N:23])=[CH:20][N:19]=2)[CH2:3][C@@H:4]1[CH3:16])(=[O:15])[CH3:14]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 67194540HCID 67194540, 화합물

생성물 1

HCID 709779596-(((2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile수율 62.5%

시약·촉매·용매 1

HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
200 °C

실험 절차

To a mixture of 1-((2S,4R)-4-amino-6-bromo-2-methyl-3,4-dihydroquinolin-1(2H)-yl)ethanone (for a preparation see Intermediate 1)(2.28 g, 8.05 mmol) and 6-chloronicotinonitrile (2.231 g, 16.10 mmol) was added NMP (20 mL) and the mixture treated with DIPEA (4.22 mL, 24.16 mmol). The mixture was split between 2 flasks and each flask was flushed with nitrogen, sealed and stirred under microwave irradiation at 200° C. for 2 h. The reaction mixtures were combined and partitioned between water and EtOAc. The aqueous layer was extracted with EtOAc (×4) and the combined organic layers were washed with water (×3), then brine and were dried (MgSO4) filtered and concentrated in vacuo. The brown solid residue was purified by chromatography (EtOAc in Hexanes gradient) to give 6-(((2S,4R)-1-acetyl-6-bromo-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (1.940 g, 5.04 mmol, 62.5% yield) as a pale yellow foam. LCMS (HpH, 2 min), Rt=1.02 min, MH+=386 (1 Br).

후처리

  1. customThe mixture was split between 2 flasks and each flask
  2. customwas flushed with nitrogen
  3. customsealed
  4. customThe reaction mixtures
  5. custompartitioned between water and EtOAc
  6. extractionThe aqueous layer was extracted with EtOAc (×4)
  7. washthe combined organic layers were washed with water (×3)
  8. dry with materialbrine and were dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe brown solid residue was purified by chromatography (EtOAc in Hexanes gradient)

출처 및 근거

ORD 기록
ord-aaa3ad66e371440a82336f90ad0dcba6
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08993554B2

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