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 1055437Notes

Reaction equation

HRID 1055437 reaction equation
[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

Participants

7

Reactant 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

Product 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)carbamateYield 53.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-b885986951a44c82890b810695a7e076
Source dataset
uspto-grants-2016_07
Patent number
US09394263B2

Reaction notes

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