1,4-Dioxane → HCID 49770164, compound

HRID 1157770Notes

Reaction equation

HRID 1157770 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]([F:32])=[C:6]2[C:10]([C:11](=[O:31])[C:12]([N:14]3[CH2:19][CH2:18][N:17]([C:20]4[N:24]([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[N:23]=[N:22][N:21]=4)[CH2:16][CH2:15]3)=[O:13])=[CH:9][NH:8][C:7]=12.C([Sn]([C:46]#[N:47])(CCCC)CCCC)CCC.[O:48]1CCOCC1>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>[F:32][C:5]1[CH:4]=[N:3][C:2]([C:46]([NH2:47])=[O:48])=[C:7]2[NH:8][CH:9]=[C:10]([C:11](=[O:31])[C:12](=[O:13])[N:14]3[CH2:19][CH2:18][N:17]([C:20]4[N:24]([C:25]5[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=5)[N:23]=[N:22][N:21]=4)[CH2:16][CH2:15]3)[C:6]=12

Participants

5

Reactant 3

HCID 312751,4-DioxaneHCID 200512Stannanecarbonitrile, tributyl-HCID 595113051-(7-bromo-4-fluoro-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione

Product 1

HCID 49770164HCID 49770164, compound

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

To a sealable flask containing 1-(7-bromo-4-fluoro-1H-pyrrolo[2,3-c]pyridin-3-yl)-2-(4-(1-phenyl-1H-tetrazol-5-yl)piperazin-1-yl)ethane-1,2-dione (1.0 g, 2.0 mmol) in 1,4-dioxane (20 mL) was added tributyltin cyanide (0.70 g, 2.2 mmol) followed by Pd(PPh3)4 (0.12 g, 0.1 mmol). The mixture was flushed with N2, and the tube was sealed and heated to 100° C. After 20 h of heating, the mixture was cooled to rt, and was diluted with MeOH (50 mL) and was filtered through a pad of celite to remove solids. To the solution was added H2O (20 mL), and the mixture was heated with a heat gun. Solids formed upon cooling, and were collected by filtration. The solids were dissolved in DMF and were purified by prep HPLC to give the title compound as an off-white solid (30 mg). LCMS: m/e 464.11 (M+H)+, ret time 1.095 min (method 3). 1H NMR (500 MHz, DMSO-D6) δ ppm 12.78 (s, 1H) 8.34 (d, J=2.14 Hz, 1H) 8.30 (s, 1H) 8.25 (d, J=3.36 Hz, 1H) 7.88 (s, 1H) 7.56-7.71 (m, 5H) 3.67-3.72 (m, 2H) 3.43-3.47 (m, 2H) 3.30-3.34 (m, 2H) 3.13-3.17 (m, 2H).

Workup

  1. customThe mixture was flushed with N2
  2. customthe tube was sealed
  3. temperatureAfter 20 h of heating
  4. temperaturethe mixture was cooled to rt
  5. additionwas diluted with MeOH (50 mL)
  6. filtrationwas filtered through a pad of celite
  7. customto remove solids
  8. additionTo the solution was added H2O (20 mL)
  9. temperaturethe mixture was heated with a heat gun
  10. customSolids formed
  11. temperatureupon cooling
  12. filtrationwere collected by filtration
  13. dissolutionThe solids were dissolved in DMF
  14. customwere purified by prep HPLC

Sources & evidence

ORD record
ord-9382b688f3f147b0b9cec411759b797b
Source dataset
uspto-grants-2010_10
Patent number
US07807676B2

Reaction notes

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