Methanol → HCID 178473712, 화합물

HRID 628951노트

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HRID 628951 반응식
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]#[CH:15])=[CH:11][CH:12]=2)[C@H:7]([NH:16][C:17]2[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][N:18]=2)[CH2:6][C@@H:5]1[CH3:25])(=[O:3])[CH3:2].CO.[N:28]([Si](C)(C)C)=[N+:29]=[N-:30]>[Cu]I.CN(C=O)C>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[N:28]=[N:29][NH:30][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:16][C:17]2[CH:24]=[CH:23][C:20]([C:21]#[N:22])=[CH:19][N:18]=2)[CH2:6][C@@H:5]1[CH3:25])(=[O:3])[CH3:2]

참가 물질

6

반응물 3

HCID 887MethanolHCID 78378Azidotrimethylsilane3회HCID 867120316-(((2S,4R)-1-acetyl-6-ethynyl-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile

생성물 1

HCID 178473712HCID 178473712, 화합물

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매2회HCID 6228Dimethylformamide용매

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온도
100 °C

실험 절차

A microwaveable vial was charged with 6-(((2S,4R)-1-acetyl-6-ethynyl-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (for a preparation see Intermediate 9) (527 mg, 1.595 mmol), Copper (I) Iodide (30 mg, 0.158 mmol), methanol (0.333 ml), DMF (3 ml). Azidotrimethylsilane (0.423 ml, 3.19 mmol) was added to the solution, the vial sealed and heated at 100° C. for 1 h (microwave). Azidotrimethylsilane (0.211 ml, 1.59 mmol) was added to the vial and the mixture heated for a further 1 h (sealed vial, microwave). Azidotrimethylsilane (0.211 ml, 1.590 mmol), and copper (I) iodide (30 mg, 0.158 mmol) was added. The vial was resealed and heated for a further 1 h. The reaction solution was concentrated in vacuo, diluted with water (15 ml) and extracted with DCM (3×10 ml). The organics were combined and dried (hydrophobic frit). The mixture was concentrated and the sample purified by chromatography on a silica cartridge (50 g) eluting with a methanol/DCM gradient (0-10%). The appropriate fractions were combined and the solvent evaporated in vacuo to give 6-(((2S,4R)-1-acetyl-2-methyl-6-(1H-1,2,3-triazol-4-yl)-1,2,3,4-tetrahydroquinolin-4-yl)amino)nicotinonitrile (50 mg). LCMS (formate): Rt 0.71 min, MH+ 374

후처리

  1. customthe vial sealed
  2. temperatureheated for a further 1 h
  3. custom(sealed vial, microwave)
  4. temperatureheated for a further 1 h
  5. concentrationThe reaction solution was concentrated in vacuo
  6. additiondiluted with water (15 ml)
  7. extractionextracted with DCM (3×10 ml)
  8. customdried (hydrophobic frit)
  9. concentrationThe mixture was concentrated
  10. customthe sample purified by chromatography on a silica cartridge (50 g)
  11. washeluting with a methanol/DCM gradient (0-10%)
  12. customthe solvent evaporated in vacuo

출처 및 근거

ORD 기록
ord-d30b042c177e4037915d8d8ae367f4c9
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09315487B2

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