Diisopropylethylamine → (S)-tert-butyl 3-bromo-1-(4-methyl-1-(methylamino)-1-oxopentan-2-ylcarbamoyl)-6,7-dihydro-5H-imidazo[1,5-a][1,4]diazepine-8(9H)-carboxylate

HRID 535967Notes

Reaction equation

HRID 535967 reaction equation
[Br:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][N:10]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:11][C:5]2=[C:4]([C:19](O)=[O:20])[N:3]=1.[CH3:22][NH:23][C:24](=[O:31])[C@H:25]([CH2:27][CH:28]([CH3:30])[CH3:29])[NH2:26].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>CN(C=O)C>[Br:1][C:2]1[N:6]2[CH2:7][CH2:8][CH2:9][N:10]([C:12]([O:14][C:15]([CH3:17])([CH3:18])[CH3:16])=[O:13])[CH2:11][C:5]2=[C:4]([C:19](=[O:20])[NH:26][C@@H:25]([CH2:27][CH:28]([CH3:30])[CH3:29])[C:24]([NH:23][CH3:22])=[O:31])[N:3]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11672684(2S)-2-amino-N,4-dimethylpentanamideHCID 576352073-bromo-8-(tert-butoxycarbonyl)-6,7,8,9-tetrahydro-5H-imidazo[1,5-a][1,4]diazepine-1-carboxylic acid

Product 1

HCID 57635572(S)-tert-butyl 3-bromo-1-(4-methyl-1-(methylamino)-1-oxopentan-2-ylcarbamoyl)-6,7-dihydro-5H-imidazo[1,5-a][1,4]diazepine-8(9H)-carboxylateYield 51%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-bromo-8-(tert-butoxycarbonyl)-6,7,8,9-tetrahydro-5H-imidazo[1,5-a][1,4]diazepine-1-carboxylic acid (33E) (1.08 g, 3.0 mmol), H-Leu-NHMe (20B) (0.62 g, 4.30 mmol) and DIEA (0.52 mL, 3.0 mmol) in DMF (25 mL) was added TBTU (1.46 g, 4.55 mmol) in two batches over 10 min at 0° C. After stirring from 0° C. to room temperature overnight, the reaction was quenched with water and evaporated under vacuum. The residue was extracted between saturated aqueous NaHCO3 and EtOAc. The organic layer was dried over anhydrous Na2SO4 and evaporated to dryness. The crude mixture was purified by column chromatography with 60% to 100% EtOAc/Hex to give an oily product 55A at 51% yield. LCMS (+ESI) m/z 486.1, 489.1 [M+H]+.

Workup

  1. customthe reaction was quenched with water
  2. customevaporated under vacuum
  3. extractionThe residue was extracted between saturated aqueous NaHCO3 and EtOAc
  4. dry with materialThe organic layer was dried over anhydrous Na2SO4
  5. customevaporated to dryness
  6. customThe crude mixture was purified by column chromatography with 60% to 100% EtOAc/Hex

Sources & evidence

ORD record
ord-b2fc43b940e54003b54569575556fbea
Source dataset
uspto-grants-2014_10
Patent number
US08859538B2

Reaction notes

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