Sodium Iodide → {(S)-1-[(2S,3S)-1-(4-acetyl-benzoyl)-5-(5-bromo-2-methoxy-naphthalen-1-ylmethyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester

HRID 1486037Notes

Reaction equation

HRID 1486037 reaction equation
[C:1]([O:5][C:6](=[O:38])[N:7]([C@H:9]([C:11](=[O:37])[NH:12][C@H:13]1[C@H:19]([CH3:20])[N:18]([C:21](=[O:31])[C:22]2[CH:27]=[CH:26][C:25]([C:28](=[O:30])[CH3:29])=[CH:24][CH:23]=2)[C:17]2[CH:32]=[CH:33][CH:34]=[CH:35][C:16]=2[NH:15][C:14]1=[O:36])[CH3:10])[CH3:8])([CH3:4])([CH3:3])[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[Br:45][C:46]1[CH:55]=[CH:54][CH:53]=[C:52]2[C:47]=1[CH:48]=[CH:49][C:50]([O:58][CH3:59])=[C:51]2[CH2:56]Cl.[I-].[Na+]>CN(C)C=O.O>[C:1]([O:5][C:6](=[O:38])[N:7]([C@H:9]([C:11](=[O:37])[NH:12][C@H:13]1[C@H:19]([CH3:20])[N:18]([C:21](=[O:31])[C:22]2[CH:23]=[CH:24][C:25]([C:28](=[O:30])[CH3:29])=[CH:26][CH:27]=2)[C:17]2[CH:32]=[CH:33][CH:34]=[CH:35][C:16]=2[N:15]([CH2:56][C:51]2[C:52]3[C:47](=[C:46]([Br:45])[CH:55]=[CH:54][CH:53]=3)[CH:48]=[CH:49][C:50]=2[O:58][CH3:59])[C:14]1=[O:36])[CH3:10])[CH3:8])([CH3:3])([CH3:4])[CH3:2]

Participants

7

Reactant 4

HCID 5238Sodium IodideHCID 10796Cesium carbonateHCID 899225115-Bromo-1-(chloromethyl)-2-methoxynaphthaleneHCID 90082668{(S)-1-[(2S,3S)-1-(4-acetyl-benzoyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester

Product 1

HCID 90082508{(S)-1-[(2S,3S)-1-(4-acetyl-benzoyl)-5-(5-bromo-2-methoxy-naphthalen-1-ylmethyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl esterYield 45.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of {(S)-1-[(2S,3S)-1-(4-acetyl-benzoyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester (60 mg, 0.115 mmol) in N,N-dimethylformamide (1.0 mL) was added cesium carbonate (94 mg, 0.287 mmol), 5-bromo-1-chloromethyl-2-methoxy-naphthalene (39.3 mg, 0.138 mmol) and sodium iodide (17.2 mg, 0.115 mmol) and the reaction was stirred for 2 h. The reaction mixture was diluted with water (10 ml) and extracted with ethyl acetate (2×15 mL). The organic layers were combined, washed with brine (1×10 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by chromatography over silica gel gradient eluted with 10 to 70% v/v ethyl acetate hexanes to give {(S)-1-[(2S,3S)-1-(4-acetyl-benzoyl)-5-(5-bromo-2-methoxy-naphthalen-1-ylmethyl)-2-methyl-4-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-ylcarbamoyl]-ethyl}-methyl-carbamic acid tert-butyl ester (40 mg, 45%).

Workup

  1. extractionextracted with ethyl acetate (2×15 mL)
  2. washwashed with brine (1×10 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by chromatography over silica gel gradient
  7. washeluted with 10 to 70% v/v ethyl acetate hexanes

Sources & evidence

ORD record
ord-bd290715a1a84501b80b702ec188f90b
Source dataset
uspto-grants-2016_08
Patent number
US09422331B2

Reaction notes

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