Sodium Iodide → tert-butyl(3S,4S)-1-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-methyl-5-(2-(methylsulfonyl)acetyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate

HRID 1486045Notes

Reaction equation

HRID 1486045 reaction equation
[CH3:1][C@@H:2]1[N:8]([C:9](=[O:15])[CH2:10][S:11]([CH3:14])(=[O:13])=[O:12])[C:7]2[CH:16]=[CH:17][CH:18]=[CH:19][C:6]=2[NH:5][C:4](=[O:20])[C@H:3]1[NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25].[Br:29][C:30]1[CH:31]=[C:32]2[C:37](=[CH:38][CH:39]=1)[C:36]([CH2:40]Cl)=[C:35]([O:42][CH3:43])[CH:34]=[CH:33]2.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>CN(C=O)C.CCOC(C)=O>[Br:29][C:30]1[CH:31]=[C:32]2[C:37](=[CH:38][CH:39]=1)[C:36]([CH2:40][N:5]1[C:4](=[O:20])[C@@H:3]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[C@H:2]([CH3:1])[N:8]([C:9](=[O:15])[CH2:10][S:11]([CH3:14])(=[O:13])=[O:12])[C:7]3[CH:16]=[CH:17][CH:18]=[CH:19][C:6]1=3)=[C:35]([O:42][CH3:43])[CH:34]=[CH:33]2

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 7371226-Bromo-1-(chloromethyl)-2-methoxynaphthaleneHCID 131736772tert-butyl(2S,3S)-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate

Product 1

HCID 131736771tert-butyl(3S,4S)-1-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-methyl-5-(2-(methylsulfonyl)acetyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamateYield 78%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a rt solution of tert-butyl(2S,3S)-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (60.3 mg, 147 μmol) in DMF (366 μl) was added 6-bromo-1-(chloromethyl)-2-methoxynaphthalene (50.2 mg, 176 μmol), cesium carbonate (62.1 mg, 191 μmol), and sodium iodide (28.6 mg, 191 μmol). The reaction was stirred at rt for 4 h, then diluted with EtOAc (30 mL), washed with H2O (30 mL) and sat. aq. NaCl (30 mL), dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash chromatography to provide tert-butyl(3S,4S)-1-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-4-methyl-5-(2-(methylsulfonyl)acetyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamate (75 mg, 78% yield) as a white solid. MS m/z 682/684 (MNa)+

Workup

  1. washwashed with H2O (30 mL) and sat. aq. NaCl (30 mL)
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-262ca1caafa342f2b44152aa0e739fc1
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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