N,N,N',N'-Tetramethylazodicarboxamide → N-(3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl)-N-(2-(7-methyl-1-oxo-1H-isoquinolin-2-yl)ethyl)-2-nitrobenzenesulfonamide

HRID 1183100Notes

Reaction equation

HRID 1183100 reaction equation
CN(C)C(N=NC(N(C)C)=O)=O.C(P(CCCC)CCCC)CCC.[CH2:26]([N:28]1[C:34](=[O:35])[C:33]([CH3:37])([CH3:36])[C:32](=[O:38])[N:31]([CH3:39])[C:30]2[CH:40]=[C:41]([O:44][CH2:45][CH2:46][CH2:47][NH:48][S:49]([C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=3[N+:58]([O-:60])=[O:59])(=[O:51])=[O:50])[CH:42]=[CH:43][C:29]1=2)[CH3:27].O[CH2:62][CH2:63][N:64]1[CH:73]=[CH:72][C:71]2[C:66](=[CH:67][C:68]([CH3:74])=[CH:69][CH:70]=2)[C:65]1=[O:75]>ClCCl.O.C1COCC1>[CH2:26]([N:28]1[C:34](=[O:35])[C:33]([CH3:37])([CH3:36])[C:32](=[O:38])[N:31]([CH3:39])[C:30]2[CH:40]=[C:41]([O:44][CH2:45][CH2:46][CH2:47][N:48]([CH2:62][CH2:63][N:64]3[CH:73]=[CH:72][C:71]4[C:66](=[CH:67][C:68]([CH3:74])=[CH:69][CH:70]=4)[C:65]3=[O:75])[S:49]([C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=3[N+:58]([O-:60])=[O:59])(=[O:51])=[O:50])[CH:42]=[CH:43][C:29]1=2)[CH3:27]

Participants

8

Reactant 4

HCID 4278N,N,N',N'-TetramethylazodicarboxamideHCID 13831TributylphosphineHCID 68672787N-(3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl)-2-nitrobenzenesulfonamideHCID 686736362-(2-hydroxyethyl)-7-methyl-2H-isoquinolin-1-one

Product 1

HCID 68672764N-(3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl)-N-(2-(7-methyl-1-oxo-1H-isoquinolin-2-yl)ethyl)-2-nitrobenzenesulfonamideYield 65%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

N,N,N′,N′-Tetra methyl azodicarboxamide (TMAD) (118 mg) and tri-n-butyl phosphine (0.17 ml) were added to a THF solution (5 ml) of N-[3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl]-2-nitrobenzenesulfonamide (231 mg) and 2-(2-hydroxyethyl)-7-methyl-2H-isoquinolin-1-one (93 mg), and stirred at room temperature overnight. Water was added to the reaction mixture, and extraction with dichloromethane was performed. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=20:1→10:1) The purified product was concentrated to dryness under reduced pressure to thereby obtain 205 mg (yield: 65%) of N-(3-(1-ethyl-3,3,5-trimethyl-2,4-dioxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-7-yloxy)propyl)-N-(2-(7-methyl-1-oxo-1H-isoquinolin-2-yl)ethyl)-2-nitrobenzenesulfonamide as a white amorphous solid.

Workup

  1. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was purified by silica gel column chromatography (ethyl acetate:methanol=20:1→10:1) The purified product
  4. concentrationwas concentrated to dryness under reduced pressure

Sources & evidence

ORD record
ord-2c75c6c8484944f5a6a8f1be9141cd4d
Source dataset
uspto-grants-2014_03
Patent number
US08664217B2

Reaction notes

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