Sodium Iodide → tert-butyl (S)-1-((S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

HRID 1055437노트

반응식

HRID 1055437 반응식
[CH3:1][N:2]([C@@H:10]([CH3:26])[C:11](=[O:25])[NH:12][C@H:13]1[CH2:19][O:18][C:17]2[CH:20]=[CH:21][CH:22]=[CH:23][C:16]=2[NH:15][C:14]1=[O:24])[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].[Br:27][C:28]1[CH:29]=[C:30]2[C:35](=[CH:36][CH:37]=1)[C:34]([CH2:38]Cl)=[C:33]([O:40][CH3:41])[CH:32]=[CH:31]2.C([O-])([O-])=O.[Cs+].[Cs+].[Na+].[I-]>CN(C=O)C.CCOC(C)=O>[Br:27][C:28]1[CH:29]=[C:30]2[C:35](=[CH:36][CH:37]=1)[C:34]([CH2:38][N:15]1[C:14](=[O:24])[C@@H:13]([NH:12][C:11](=[O:25])[C@@H:10]([N:2]([CH3:1])[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:6])[CH3:7])[CH3:26])[CH2:19][O:18][C:17]3[CH:20]=[CH:21][CH:22]=[CH:23][C:16]1=3)=[C:33]([O:40][CH3:41])[CH:32]=[CH:31]2

참가 물질

7

반응물 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 7371226-Bromo-1-(chloromethyl)-2-methoxynaphthaleneHCID 72713380tert-Butyl methyl((S)-1-oxo-1-((S)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)propan-2-yl)carbamate

생성물 1

HCID 72713381tert-butyl (S)-1-((S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate수율 53.9%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of tert-butyl methyl((S)-1-oxo-1-((S)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)propan-2-yl)carbamate (1.1 g, 3.03 mmol, Eq: 1.00) (Example 1), 6-bromo-1-(chloromethyl)-2-methoxynaphthalene (951 mg, 3.33 mmol, Eq: 1.10), Cs2CO3 (1.08 g, 3.33 mmol, Eq: 1.10), and NaI (499 mg, 3.33 mmol, Eq: 1.1) in DMF (20 mL) was stirred for 3.5 at RT then heated at 50° C. for 1 h then at 60° C. for 30 min. The mixture was cooled, diluted with EtOAc, washed with water and brine. The organic solution was dried over Na2SO4 and concentrated. The residue was purified by silica gel chromatography to afford tert-butyl (S)-1-((S)-5-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-oxo-2,3,4,5-tetrahydrobenzo[b][1,4]oxazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (1.00 g, 1.63 mmol, 53.9%) as a light yellow foam.

후처리

  1. temperaturethen heated at 50° C. for 1 h
  2. temperatureThe mixture was cooled
  3. washwashed with water and brine
  4. dry with materialThe organic solution was dried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by silica gel chromatography

출처 및 근거

ORD 기록
ord-b885986951a44c82890b810695a7e076
출처 데이터셋
uspto-grants-2016_07
특허 번호
US09394263B2

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