Dimethylformamide → 1-methylethyl ((2S,4R)-1-acetyl-6-{1-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1H-1,2,3-triazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

HRID 2366873노트

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HRID 2366873 반응식
[CH3:1][CH:2]([O:4][C:5](=[O:23])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[CH:18])[CH:15]=2)[N:10]([C:19](=[O:21])[CH3:20])[C@@H:9]([CH3:22])[CH2:8]1)[CH3:3].CN(C)C=O.[N:29]([CH2:32][CH2:33][NH:34][C:35](=[O:41])[O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[N+:30]=[N-:31]>[Cu]I.CO>[CH3:3][CH:2]([O:4][C:5](=[O:23])[NH:6][C@H:7]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([C:17]3[N:31]=[N:30][N:29]([CH2:32][CH2:33][NH:34][C:35]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:41])[CH:18]=3)[CH:15]=2)[N:10]([C:19](=[O:21])[CH3:20])[C@@H:9]([CH3:22])[CH2:8]1)[CH3:1]

참가 물질

6

반응물 3

HCID 6228DimethylformamideHCID 22323692tert-Butyl (2-azidoethyl)carbamateHCID 86669236HCID 86669236, 화합물

생성물 1

HCID 681854041-methylethyl ((2S,4R)-1-acetyl-6-{1-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1H-1,2,3-triazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate수율 85%

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 887Methanol용매

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온도
100 °C

실험 절차

A flask was charged with 1-methylethyl[(2S,4R)-1-acetyl-6-ethynyl-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (for a preparation, see Intermediate 58) (80 mg, 0.254 mmol) and copper(I) iodide (2.423 mg, 0.013 mmol) then filled with N,N-dimethylformamide (DMF) (1.8 mL) and methanol (0.200 mL). 1,1-Dimethylethyl (2-azidoethyl)carbamate (for a preparation, see Intermediate 78) (95 mg, 0.509 mmol) was added and the resulting mixture was stirred under microwave irradiation at 100° C. for 2 h then cooled to room temperature. The reaction mixture was partitioned between EtOAc and brine and the layers were separated. The aqueous phase was extracted with EtOAc (3×) and the combined organic phases were washed with brine, dried over a Na2SO4 cartridge and concentrated in vacuo. Purification of the residue on SP4 using a 10 G silica cartridge (gradient: 5 to 25% (10% MeOH in DCM) in DCM) gave 1-methylethyl((2S,4R)-1-acetyl-6-{1-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1H-1,2,3-triazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (108 mg, 0.216 mmol, 85% yield) as a pale yellow foam. LCMS (method A): Retention time 0.95 min, [M+H]+=501.26

후처리

  1. customfor a preparation
  2. additionwas added
  3. temperaturethen cooled to room temperature
  4. customThe reaction mixture was partitioned between EtOAc and brine
  5. customthe layers were separated
  6. extractionThe aqueous phase was extracted with EtOAc (3×)
  7. washthe combined organic phases were washed with brine
  8. dry with materialdried over a Na2SO4 cartridge
  9. concentrationconcentrated in vacuo
  10. customPurification of the residue on SP4

출처 및 근거

ORD 기록
ord-5719e8a666cb4be6893cfc958f071a20
출처 데이터셋
uspto-grants-2014_04
특허 번호
US08697725B2

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