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

HRID 1486059Notes

Reaction equation

HRID 1486059 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][C:5]([N:7]1[C@@H:13]([CH3:14])[C@H:12]([NH:15][C:16](=[O:28])[C@@H:17]([N:19]([CH3:27])[C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])[CH3:18])[C:11](=[O:29])[NH:10][C:9]2[CH:30]=[CH:31][CH:32]=[CH:33][C:8]1=2)=[O:6].[Br:34][C:35]1[CH:36]=[C:37]2[C:42](=[CH:43][CH:44]=1)[C:41]([CH2:45]Cl)=[C:40]([O:47][CH3:48])[CH:39]=[CH:38]2.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>CN(C=O)C.CCOC(C)=O>[Br:34][C:35]1[CH:36]=[C:37]2[C:42](=[CH:43][CH:44]=1)[C:41]([CH2:45][N:10]1[C:11](=[O:29])[C@@H:12]([NH:15][C:16](=[O:28])[C@@H:17]([N:19]([CH3:27])[C:20](=[O:26])[O:21][C:22]([CH3:24])([CH3:25])[CH3:23])[CH3:18])[C@H:13]([CH3:14])[N:7]([C:5](=[O:6])[CH2:4][CH2:3][O:2][CH3:1])[C:8]3[CH:33]=[CH:32][CH:31]=[CH:30][C:9]1=3)=[C:40]([O:47][CH3:48])[CH:39]=[CH:38]2

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 7371226-Bromo-1-(chloromethyl)-2-methoxynaphthaleneHCID 118292643tert-butyl(S)-1-((2S,3S)-1-(3-methoxypropanoyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

Product 1

HCID 118292676tert-butyl(S)-1-((3S,4S)-1-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-5-(3-methoxypropanoyl)-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamateYield 74%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a rt solution of tert-butyl(S)-1-((2S,3S)-1-(3-methoxypropanoyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (46 mg, 99.5 μmol) in DMF (249 μl) was added 6-bromo-1-(chloromethyl)-2-methoxynaphthalene (34.1 mg, 119 μmol), cesium carbonate (42.1 mg, 129 μmol), and sodium iodide (19.4 mg, 129 μmol). The reaction was stirred at rt for 16 h, then diluted with EtOAc, washed with H2O and sat. aq. NaCl, dried over Na2SO4, filtered, and concentrated. The crude material was purified by flash chromatography to provide tert-butyl(S)-1-((3S,4S)-1-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-5-(3-methoxypropanoyl)-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (52.4 mg, 74%) as a white solid. MS m/z 733/735 (MNa)+.

Workup

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

Sources & evidence

ORD record
ord-1c1fa1e87f0347c1993247e165474045
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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