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Structure of 1082674-24-5

Chemical Structure| 1082674-24-5

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Product Details of [ 1082674-24-5 ]

CAS No. :1082674-24-5
Formula : C10H5BrN2
M.W : 233.06
SMILES Code : N#CC1=NC=CC2=C1C=CC(Br)=C2
MDL No. :MFCD18633063
InChI Key :NOTGHQFEQASFGA-UHFFFAOYSA-N
Pubchem ID :77174826

Safety of [ 1082674-24-5 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Application In Synthesis of [ 1082674-24-5 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 1082674-24-5 ]

[ 1082674-24-5 ] Synthesis Path-Downstream   1~4

  • 1
  • potassium phosphate [ No CAS ]
  • [ 1082674-24-5 ]
  • [ 76144-87-1 ]
  • [ 23687-26-5 ]
YieldReaction ConditionsOperation in experiment
25.4% With tris-(dibenzylideneacetone)dipalladium(0); In dimethyl sulfoxide; ethyl acetate; Petroleum ether; Step 3. Synthesis of 6-amino isoquinoline (#E3). A solution of #A2 (4.0 g, 51.7 mmol), 6-bromoisoquinoline-1-carbonitrile #A3 (6.0 g, 25.9 mmol), BINAP (3.2 g, 5.2 mmol), Pd2(dba)3 (2.3 g, 2.6 mmol) and potassium phosphate (11.0 g, 51.7 mmol) in anhydrous DMSO (35 mL) was heated at 80° C. for 2 h. The complete disappearance of the 6-bromoisoquinoline-1-carbonitrile #A3 was observed on TLC. The reaction mixture was cooled to room temperature, filtered through Celite? pad and the filtrate was diluted with water (100 mL). The mixture was extracted with EtOAc (100 mL*3). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude material which was purified by silica gel (100-200 mesh) column chromatography using 40percent EtOAc in petroleum ether as an eluting system to give #E3 as yellow solid (1.5 g, 25.4percent). Rf: 0.4 (60percent EtOAc in petroleum ether). LCMS m/z=227.9 (M+H); 1H NMR (400 MHz, d6-DMSO): delta 1.18 (d, J=6.8 Hz, 3H), 3.36-3.47 (m, 1H), 3.48-3.53 (m, 1H), 3.60-3.66 (m, 1H), 6.80-6.82 (m, 2H), 7.32 (dd, J=2.4 Hz, 8.8 Hz, 1H), 7.72 (d, J=5.6 Hz, 1H), 7.87 (d, J=9.6 Hz, 1H), 8.30 (d, J=5.6 Hz, 1H).
24.3% With tris-(dibenzylideneacetone)dipalladium(0); In dimethyl sulfoxide; Step 3. Synthesis of 6-amino isoquinoline (#F3). A solution of #F2 (4.5 g, 51.7 mmol), 6-bromoisoquinoline-1-carbonitrile (6.0 g, 25.9 mmol), BINAP (3.2 g, 5.1 mmol), Pd2(dba)3 (2.3 g, 2.6 mmol) and potassium phosphate (11.0 g, 51.7 mmol) in anhydrous DMSO (35 mL) was heated at 80° C. for 2 h. The complete disappearance of the 6-bromoisoquinoline-1-carbonitrile was observed on TLC. The reaction mixture was cooled to room temperature, filtered through a Celite? pad and the filtrate was diluted with water (100 mL). The mixture was extracted with EtOAc (100 mL*3). The combined organic layers were dried over anhydrous sodium sulfate and concentrated under reduced pressure to give crude material. The product was purified by chromatography on silica gel (100-200 mesh) using 10percent MeOH in DCM as eluant to give racemic #F3 as yellow solid (1.5 g, 24.3percent). Rf: 0.4 (50percent EtOAc in petroleum ether). Chiral HPLC: two enantiomers (61.0percent, 39.0percent). LCMS m/z=240.1 (M+H). H NMR (400 MHz, d6-DMSO): delta 2.19-2.27 (m, 1H), 2.36-2.45 (m, 1H), 3.67-3.84 (m, 3H), 4.02-4.07 (m, 1H), 4.33-4.39 (m, 1H), 5.09 (t, J=4.8 Hz, 1H), 6.83 (d, J=1.6 Hz, 1H), 7.33 (dd, J=8.8 Hz, J=2.0 Hz, 1H), 7.78 (d, J=6.4 Hz, 1H), 7.97 (d, J=8.8 Hz, 1H), 8.36 (d, J=5.6 Hz, 1H).
  • 2
  • [ 15518-10-2 ]
  • [ 1082674-24-5 ]
  • 6-(3-hydroxy-2-methylpropylamino)isoquinoline-1-carbonitrile [ No CAS ]
YieldReaction ConditionsOperation in experiment
48.5% With potassium phosphate; tris-(dibenzylideneacetone)dipalladium(0); 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In dimethyl sulfoxide; at 105℃; for 2h;Inert atmosphere; K3P04 (6.1 g, 28.8 mmol), BINAP (0.44 g, 0.72 mmol) and Pd2(dba)3 (0.32.0 g, 0.36 mmol) was added to the degassed suspension of 6-bromo-1 -cyanoisoquinoline A3 (1.7 g, 7.2 mmol), D2 (1.2 g, 14.5 mmol) in DMSO at room temperature. The reaction mixture was heated at 105 C for 2 h. The reaction was cooled to room temperature, water (500 ml_) followed by EtOAc (100 ml_) were added, and the mixture was stirred for 10 minutes. The biphasic mixture was filtered through a Celite pad and washed with EtOAc (100 ml_). The organic layer was separated, and the aqueous layer was extracted with EtOAc (3 x 100 ml_). The combined organic layers were dried over anhydrous Na2S04, concentrated under reduced pressure to get a crude material. This was purified by column chromatography on 100 - 200 mesh silica gel, using 50 - 70% EtOAc in petroleum ether as the eluent to obtain D3 (0.5 g, 48.5%) as a yellow solid. Rf: 0.4 (60% EtOAC in petroleum ether). LCMS m/z = 242.0 (M + H). 1 H NMR (400 MHz, cf6-DMSO): delta 0.97 (d, J = 6.4 Hz, 3H), 1.87 - 1.99 (m, 1 H), 2.92 - 2.99 (m, 1 H), 3.20 - 3.27 (m, 1 H), 3.38 - 3.42 (m, 2H), 4.59 (t, J = 5.2 Hz, 1 H), 6.77 (d, J = 2.0, 1 H), 7.01 (t, J = 5.6 Hz, 1 H), 7.34 (dd, J = 9.2 Hz, J = 2.0 Hz, 1 H), 7.73 (d, J = 6.0 Hz, 1 H), 7.88 (d, J = 8.8 Hz, 1 H), 8.312 (d, J = 6.0 Hz, 1 H).
  • 3
  • [ 15518-10-2 ]
  • [ 1082674-24-5 ]
  • 6-(3-hydroxy-2-methylpropylamino)isoquinoline-1-carbonitrile [ No CAS ]
  • C24H19N5O [ No CAS ]
  • 4
  • [ 1082674-24-5 ]
  • [ 498-63-5 ]
  • C15H15N3O [ No CAS ]
  • C15H15N3O [ No CAS ]
YieldReaction ConditionsOperation in experiment
With tris-(dibenzylideneacetone)dipalladium(0); caesium carbonate; 2,2'-bis-(diphenylphosphino)-1,1'-binaphthyl; In toluene; at 110℃; for 3h;Inert atmosphere; Pd2(dba)3 (350 mg, 0.06 mmol), BINAP (790.0 mg, 0.2 mmol), Cs2C03 (6.2 g, 3.0 mmol) were added to a mixture of 6- bromoisoquinoline-1 -carbonitrile A3 (1.5 g, 6.4 mmol) and K1 (1.3 g, 12.8 mmol) in toluene (10 mL) under nitrogen atmosphere. The reaction mixture was heated to 1 10 °C for 3 h. The mixture was diluted with EtOAc and washed with water and brine solution. Organic layer was dried over Na2S04 and concentrated to give crude material. The crude material was purified by column chromatography on silica gel (100 - 200 mesh) eluted with 40percent EtOAc in petroleum ether to give racemic material (K2, K3, 1 g, 33percent). The isomers were separated by chiral preparative HPLC to give K2 (500 mg) and K3 (450 mg). Rf: 0.2 (EtOAc).
 

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