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

HRID 1486063Notes

Reaction equation

HRID 1486063 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][CH:29]=[CH:30][C:5]1=2)(=[O:3])[CH3:2].Br[CH2:32][C:33]1[C:41]2[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=2)[N:35]([C:42]2[CH:49]=[CH:48][CH:47]=[CH:46][C:43]=2[C:44]#[N:45])[N:34]=1.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]([CH3:22])([CH3:21])[CH3:20])[CH3:15])[C:8](=[O:26])[N:7]([CH2:32][C:33]2[C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[N:35]([C:42]3[CH:49]=[CH:48][CH:47]=[CH:46][C:43]=3[C:44]#[N:45])[N:34]=2)[C:6]2[CH:27]=[CH:28][CH:29]=[CH:30][C:5]1=2)(=[O:3])[CH3:2]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 900376452-(3-Bromomethyl-indazol-1-yl)-benzonitrileHCID 118292585tert-butyl(S)-1-((2S,3S)-1-acetyl-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1, 4]diazepin-3-ylamino)-1-ox opropan-2-yl(methyl)carbamate

Product 1

HCID 118292660tert-butyl(S)-1-((2S,3S)-1-acetyl-5-((1-(2-cyanophenyl)-1H-indazol-3-yl)methyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamateYield 60.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a rt solution of tert-butyl(S)-1-((2S,3S)-1-acetyl-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (84.6 mg, 202 μmol) in DMF (505 μl) was added 2-(3-(bromomethyl)-1H-indazol-1-yl)benzonitrile (75.7 mg, 243 μmol), cesium carbonate (85.6 mg, 263 μmol), and sodium iodide (39.4 mg, 263 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-((2S,3S)-1-acetyl-5-((1-(2-cyanophenyl)-1H-indazol-3-yl)methyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylamino)-1-oxopropan-2-yl(methyl)carbamate (79 mg, 60%) as a white solid. MS m/z 672 (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-59ce6216423047659d34e2ab9243e31d
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

Loading…