(S)-tert-Butyl (3-(benzyloxy)-1-(5-bromo-3-(3,5-difluorophenyl)-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)propyl)carbamate → (S)-tert-Butyl (3-(benzyloxy)-1-(5-cyano-3-(3,5-difluorophenyl)-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)propyl)carbamate

HRID 1052364Notes

Reaction equation

HRID 1052364 reaction equation
[CH2:1]([O:8][CH2:9][CH2:10][C@H:11]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:12]1[N:17]([C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=2)[C:16](=[O:26])[C:15]2=[C:27](Br)[CH:28]=[CH:29][N:14]2[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:39]([Zn]C#N)#[N:40]>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([O:8][CH2:9][CH2:10][C@H:11]([NH:31][C:32](=[O:38])[O:33][C:34]([CH3:37])([CH3:36])[CH3:35])[C:12]1[N:17]([C:18]2[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=2)[C:16](=[O:26])[C:15]2=[C:27]([C:39]#[N:40])[CH:28]=[CH:29][N:14]2[N:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 2

HCID 131736114(S)-tert-Butyl (3-(benzyloxy)-1-(5-bromo-3-(3,5-difluorophenyl)-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)propyl)carbamateHCID 178514179HCID 178514179, compound

Product 1

HCID 131736115(S)-tert-Butyl (3-(benzyloxy)-1-(5-cyano-3-(3,5-difluorophenyl)-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)propyl)carbamateYield 79.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

In a reactor vessel (S)-tert-butyl (3-(benzyloxy)-1-(5-bromo-3-(3,5-difluorophenyl)-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)propyl)carbamate (0.81 g, 1.37 mmol) was dissolved in 32 mL dimethylformamide. Dicyanozinc (0.4 g, 3.49 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.64 g, 0.55 mmol) were added under argon conditions. The reaction was stirred at 120° C. overnight. The crude was filtered through a plug of Celite and washed several times with ethyl acetate. The combinated filtrates were evaporated and washed with water, brine, dried over sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified using SP1 ® Purification System (0% to 40%, hexane-ethyl acetate) to obtain 0.58 g (77% yield) of the title compound as a white solid. Purity 98%.

Workup

  1. filtrationThe crude was filtered through a plug of Celite
  2. washwashed several times with ethyl acetate
  3. customThe combinated filtrates were evaporated
  4. washwashed with water, brine
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified
  9. customSP1 ® Purification System (0% to 40%, hexane-ethyl acetate)

Sources & evidence

ORD record
ord-a37610a698d04cf0b77edd0d5a05d735
Source dataset
uspto-grants-2016_07
Patent number
US09388189B2

Reaction notes

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