Sodium hydride → 3-(4-fluoro-phenyl)-4H,6H-1,2,5,10b-tetraaza-benzo[e]azulene-5-carboxylic acid tert-butyl ester

HRID 1253900Notes

Reaction equation

HRID 1253900 reaction equation
[H-].[Na+].[C:3]([O:7][C:8](=[O:20])[NH:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[N:17]=[N+:18]=[N-:19])([CH3:6])([CH3:5])[CH3:4].Br[CH2:22][C:23]#[C:24][C:25]1[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=1>CCCCCC.CN(C=O)C>[C:3]([O:7][C:8]([N:9]1[CH2:22][C:23]2[N:17]([N:18]=[N:19][C:24]=2[C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH2:10]1)=[O:20])([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 105605241-(3-Bromoprop-1-yn-1-yl)-4-fluorobenzeneHCID 59176460Tert-butyl 2-azidobenzylcarbamate

Product 1

HCID 687803143-(4-fluoro-phenyl)-4H,6H-1,2,5,10b-tetraaza-benzo[e]azulene-5-carboxylic acid tert-butyl esterYield 18.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8058HexaneSolvent

Procedure

Sodium hydride (80.0 mg, 2.0 mmol; 60% suspension in mineral oil) was washed with hexane (2 mL) in a flame dried round bottomed flask under nitrogen atmosphere. To the resulting free floating powder, was added a solution of (2-azido-benzyl)-carbamic acid tert-butyl ester (250 mg, 1.0 mmol) in dry DMF (3 mL) dropwise at 0° C. under nitrogen atmosphere. The reaction mixture was stirred at this temperature for 30 min followed by dropwise addition of a solution of 1-(3-bromo-prop-1-ynyl)-4-fluoro-benzene (318.0 mg, 1.50 mmol) in dry DMF (1.5 mL). The reaction mixture was stirred at r.t. for 2 h. After the completion of the reaction as confirmed by TLC, the crude compound was extracted with ethylacetate (2×10 mL). The combined organic layer was washed with water (2×10 mL). Organic layer was separated, dried over Na2SO4 and concentrated in vacuo to afford the crude compound which was purified by column chromatography (silica gel, 1:9 EtOAc:Pet.Ether) to afford 3-(4-fluoro-phenyl)-4H,6H-1,2,5,10b-tetraaza-benzo[e]azulene-5-carboxylic acid tert-butyl ester (70 mg, 12.2%) as a viscous oil.

Workup

  1. customdried round bottomed flask under nitrogen atmosphere
  2. stirringThe reaction mixture was stirred at r.t. for 2 h
  3. customAfter the completion of the reaction
  4. extractionthe crude compound was extracted with ethylacetate (2×10 mL)
  5. washThe combined organic layer was washed with water (2×10 mL)
  6. customOrganic layer was separated
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customto afford the crude compound which
  10. customwas purified by column chromatography (silica gel, 1:9 EtOAc:Pet.Ether)

Sources & evidence

ORD record
ord-91baf0e687754c1d9821ed2e21b9de52
Source dataset
uspto-grants-2013_06
Patent number
US08455479B2

Reaction notes

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