Sodium Iodide → tert-butyl(S)-1-((3S,4S)-1-((5-bromo-2-methoxynaphthalen-1-yl)methyl)-7-cyano-4-methyl-5-(2-(methylsulfonyl)acetyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate

HRID 1486093Notes

Reaction equation

HRID 1486093 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[NH:12][C:11](=[O:13])[C@@H:10]([NH:14][C:15](=[O:27])[C@@H:16]([N:18]([CH3:26])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:23])[CH3:22])[CH3:17])[C@H:9]([CH3:28])[N:8]([C:29](=[O:35])[CH2:30][S:31]([CH3:34])(=[O:33])=[O:32])[C:7]=2[CH:36]=1)#[N:2].[Br:37][C:38]1[CH:47]=[CH:46][CH:45]=[C:44]2[C:39]=1[CH:40]=[CH:41][C:42]([O:50][CH3:51])=[C:43]2[CH2:48]Cl.C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>CN(C=O)C.CCOC(C)=O>[Br:37][C:38]1[CH:47]=[CH:46][CH:45]=[C:44]2[C:39]=1[CH:40]=[CH:41][C:42]([O:50][CH3:51])=[C:43]2[CH2:48][N:12]1[C:11](=[O:13])[C@@H:10]([NH:14][C:15](=[O:27])[C@@H:16]([N:18]([CH3:26])[C:19](=[O:25])[O:20][C:21]([CH3:24])([CH3:22])[CH3:23])[CH3:17])[C@H:9]([CH3:28])[N:8]([C:29](=[O:35])[CH2:30][S:31]([CH3:34])(=[O:32])=[O:33])[C:7]2[CH:36]=[C:3]([C:1]#[N:2])[CH:4]=[CH:5][C:6]1=2

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 72713840tert-butyl(S)-1-((2S,3S)-8-cyano-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamateHCID 899225115-Bromo-1-(chloromethyl)-2-methoxynaphthalene

Product 1

HCID 118292656tert-butyl(S)-1-((3S,4S)-1-((5-bromo-2-methoxynaphthalen-1-yl)methyl)-7-cyano-4-methyl-5-(2-(methylsulfonyl)acetyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamateYield 76%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a rt solution of tert-butyl(S)-1-((2S,3S)-8-cyano-2-methyl-1-(2-(methylsulfonyl)acetyl)-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (29.5 mg, 56.6 μmol) in DMF (141 μl) was added 5-bromo-1-(chloromethyl)-2-methoxynaphthalene (17.8 mg, 62.2 μmol), cesium carbonate (22.1 mg, 67.9 μmol), and sodium iodide (10.2 mg, 67.9 μmol). The reaction was stirred at rt for 2.5 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-((5-bromo-2-methoxynaphthalen-1-yl)methyl)-7-cyano-4-methyl-5-(2-(methylsulfonyl)acetyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (33 mg, 76%) as a white solid. MS m/z 792/794 (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-245cb6f3e0e14515af6fad83624ac4b4
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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