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

HRID 1486103Notes

Reaction equation

HRID 1486103 reaction equation
[C:1]([N:4]1[C@@H:10]([CH3:11])[C@H:9]([NH:12][C:13](=[O:25])[C@@H:14]([N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH3:15])[C:8](=[O:26])[NH:7][C:6]2[CH:27]=[CH:28][C:29]([C:31]#[N:32])=[CH:30][C:5]1=2)(=[O:3])[CH3:2].Cl[CH2:34][C:35]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[CH:38]=[CH:37][C:36]=1[O:45][CH3:46].C(=O)([O-])[O-].[Cs+].[Cs+].[I-].[Na+]>CN(C=O)C.CCOC(C)=O>[C:1]([N:4]1[C@@H:10]([CH3:11])[C@H:9]([NH:12][C:13](=[O:25])[C@@H:14]([N:16]([CH3:24])[C:17](=[O:23])[O:18][C:19]([CH3:21])([CH3:20])[CH3:22])[CH3:15])[C:8](=[O:26])[N:7]([CH2:34][C:35]2[C:44]3[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=3)[CH:38]=[CH:37][C:36]=2[O:45][CH3:46])[C:6]2[CH:27]=[CH:28][C:29]([C:31]#[N:32])=[CH:30][C:5]1=2)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 133566461-(Chloromethyl)-2-methoxynaphthaleneHCID 90088957tert-butyl(S)-1-((2S,3S)-1-acetyl-8-cyano-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 72712575tert-butyl(S)-1-((3S,4S)-5-acetyl-7-cyano-1-((2-methoxynaphthalen-1-yl)methyl)-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1, 4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamateYield 82%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a rt solution of tert-butyl(S)-1-((2S,3S)-1-acetyl-8-cyano-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (53 mg, 120 μmol) in DMF (299 μl) was added 1-(chloromethyl)-2-methoxynaphthalene (29.6 mg, 143 μmol), cesium carbonate (50.6 mg, 155 μmol), and sodium iodide (23.3 mg, 155 μmol). The reaction was stirred at rt for 1 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)-5-acetyl-7-cyano-1-((2-methoxynaphthalen-1-yl)methyl)-4-methyl-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (60 mg, 82%) as a white solid. MS m/z 636 (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-533486bf0fda4297be3c7692ac4efe18
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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