Sodium Iodide → tert-butyl(S)-1-((3S,4S)-1-((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-ylamino)-1-oxopropan-2-yl(methyl)carbamate

HRID 1486052Notes

Reaction equation

HRID 1486052 reaction equation
[CH3:1][N:2]([C@@H:10]([CH3:34])[C:11]([NH:13][C@H:14]1[C@H:20]([CH3:21])[N:19]([C:22](=[O:28])[CH2:23][S:24]([CH3:27])(=[O:26])=[O:25])[C:18]2[CH:29]=[CH:30][CH:31]=[CH:32][C:17]=2[NH:16][C:15]1=[O:33])=[O:12])[C:3](=[O:9])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6].Cl[CH2:36][C:37]1[C:46]2[C:41](=[CH:42][CH:43]=[CH:44][CH:45]=2)[CH:40]=[CH:39][C:38]=1[O:47][CH3:48].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>CN(C=O)C.CCOC(C)=O>[CH3:48][O:47][C:38]1[CH:39]=[CH:40][C:41]2[C:46](=[CH:45][CH:44]=[CH:43][CH:42]=2)[C:37]=1[CH2:36][N:16]1[C:15](=[O:33])[C@@H:14]([NH:13][C:11](=[O:12])[C@@H:10]([N:2]([CH3:1])[C:3](=[O:9])[O:4][C:5]([CH3:6])([CH3:7])[CH3:8])[CH3:34])[C@H:20]([CH3:21])[N:19]([C:22](=[O:28])[CH2:23][S:24]([CH3:27])(=[O:25])=[O:26])[C:18]2[CH:29]=[CH:30][CH:31]=[CH:32][C:17]1=2

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 133566461-(Chloromethyl)-2-methoxynaphthaleneHCID 90082560tert-butyl methyl((S)-1-((2S,3S)-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)carbamate

Product 1

HCID 118292694tert-butyl(S)-1-((3S,4S)-1-((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-ylamino)-1-oxopropan-2-yl(methyl)carbamateYield 80%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a rt solution of tert-butyl methyl((S)-1-((2S,3S)-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)carbamate (141 mg, 284 μmol) in DMF (710 μl) was added 1-(chloromethyl)-2-methoxynaphthalene (64.6 mg, 312 μmol), cesium carbonate (111 mg, 341 μmol), and sodium iodide (51.1 mg, 341 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-((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-ylamino)-1-oxopropan-2-yl(methyl)carbamate (151 mg, 80%) as a white solid. MS m/z 689 (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-ecd3d0759d0c4d7793dde98e10b67f73
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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