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 1055437Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1055437
[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

Komponenten

7

Edukt 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

Produkt 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)carbamateAusbeute 53,9 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-b885986951a44c82890b810695a7e076
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394263B2

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