Sodium bis(trimethylsilyl)amide → N-benzyl-N-isopropyl-2-(5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-acetamide

HRID 900135Notes

Reaction equation

HRID 900135 reaction equation
[C:1]1([C:7]2[N:16]3[C:10]([CH2:11][C:12](=[O:21])[NH:13][C:14]4[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=43)=[N:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH2:32]([N:39]([CH:44]([CH3:46])[CH3:45])[C:40](=[O:43])[CH2:41]Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>CN(C=O)C.P([O-])([O-])([O-])=O>[CH2:32]([N:39]([CH:44]([CH3:46])[CH3:45])[C:40](=[O:43])[CH2:41][N:13]1[C:12](=[O:21])[CH2:11][C:10]2[N:16]([C:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[N:8][N:9]=2)[C:15]2[CH:17]=[CH:18][CH:19]=[CH:20][C:14]1=2)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

6

Reactant 3

HCID 2724254Sodium bis(trimethylsilyl)amideHCID 103560791-Phenyl-4h-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5(6h)-one2×HCID 15216006N-benzyl-2-bromo-N-propan-2-ylacetamide

Product 1

HCID 58957935N-benzyl-N-isopropyl-2-(5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-acetamide

Reagents, catalysts & solvents 2

HCID 1061PhosphateSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a solution of 1-phenyl-4H,6H-2,3,6,10b-tetraaza-benzo[e]azulen-5-one (Preparation 4(A) (30.0 g, 108 mmol) in DMF (200 mL) at 0° C. was added NaHMDS (1.0M in THF, 13.6 g, 118 mmol) and N-benzyl-2-bromo-N-isopropyl-acetamide (Preparation 1(C) (35.2, 130 mmol) in DMF (25 mL). The reaction was stirred at room temperature for 24 hours and was diluted with a pH 6.8 phosphate buffer. The aqueous solution was washed with EtOAc (3×). The combined organic solutions were washed with brine (3×), dried (Na2SO4), filtered and concentrated. Purification by medium pressure chromatography eluting with a solvent gradient (CH2Cl2 to 12% acetone in CH2Cl2) provided 13.9 g of N-benzyl-N-isopropyl-2-(5-oxo-1-phenyl-4,5-dihydro-2,3,6,10b-tetraaza-benzo[e]azulen-6-yl)-acetamide. 1H NMR (CDCl3) δ 7.64-7.55 (m, 2H), 7.44-7.08 (m, 11H), 6.89 (m, 1H), 4.96-4.08 (m, 6H), 3.57 (m, 1H), 1.17 (m, 6H).

Workup

  1. washThe aqueous solution was washed with EtOAc (3×)
  2. washThe combined organic solutions were washed with brine (3×)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by medium pressure chromatography
  7. washeluting with a solvent gradient (CH2Cl2 to 12% acetone in CH2Cl2)

Sources & evidence

ORD record
ord-8530f2d1a4a44cc48ef995be68e30069
Source dataset
uspto-grants-2008_04
Patent number
US07358242B2

Reaction notes

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