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Ethanol → Bcr-abl1-IN-1

HRID 629118
Notes
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Reaction equation

HRID 629118 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([CH:21]=1)[C:7]([NH:9][C:10]1[CH:15]=[CH:14][C:13]([O:16][C:17]([F:20])([F:19])[F:18])=[CH:12][CH:11]=1)=[O:8].[N:22]1[CH:27]=[CH:26][CH:25]=[C:24](B(O)O)[CH:23]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].CCO>C1COCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C1(C)C=CC=CC=1.O>[F:18][C:17]([F:20])([F:19])[O:16][C:13]1[CH:14]=[CH:15][C:10]([NH:9][C:7]([C:6]2[CH:21]=[C:2]([C:24]3[CH:23]=[N:22][CH:27]=[CH:26][CH:25]=3)[CH:3]=[N:4][CH:5]=2)=[O:8])=[CH:11][CH:12]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

9

Reactant 4

HCID 702EthanolHCID 62657Potassium Phosphate, TribasicHCID 27343783-Pyridinylboronic acidHCID 46840185-bromo-N-(4-(trifluoromethoxy)phenyl)nicotinamide

Product 1

HCID 72201584Bcr-abl1-IN-1

Reagents, catalysts & solvents 4

HCID 44119782
Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)
Catalyst
HCID 962WaterSolvent
HCID 1140TolueneSolvent
HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 5-bromo-N-(4-(trifluoromethoxy)phenyl)nicotinamide (Stage 42.1, 5 g, 13.85 mmol), 3-pyridylboronic acid (1.872 g, 15.23 mmol), PdCl2(dppf) (0.507 g, 0.692 mmol), K3PO4 (8.82 g, 41.5 mmol), EtOH (9.33 mL), water (14 mL) and toluene (70 mL) was stirred at 100° C. for 2 h. The solvent was evaporated off under reduced pressure and the residue was treated with water and extracted with EtOAc. The combined extracts were washed with water and brine, dried over Na2SO4 and the solvent was evaporated off under reduced pressure. The residue was purified by flash chromatography (Silica gel column, 500 g, EtOAc/MeOH from 0 to 2% MeOH). Fractions containing the pure product were combined and the solvent was evaporated off under reduced pressure to give a residue which was dissolved in THF, stirred overnight with Si-Thiol (1 g), filtered and the filtrate was evaporated off under reduced pressure to give the title compound as a white solid. UPLC-MS (Condition 7) tR 0.95 min, m/z=358 [M−H]−; 1H-NMR (400 MHz, DMSO-d6) δ ppm 7.41 (d, J=8.56 Hz, 2H) 7.59 (dd, J=7.95, 4.77 Hz, 1H) 7.91 (m, J=9.00 Hz, 2H) 8.29 (dt, J=7.83, 1.96 Hz, 1H) 8.65 (t, J=2.20 Hz, 1H) 8.68 (dd, J=4.77, 1.59 Hz, 1H) 9.08 (d, J=1.96 Hz, 1H) 9.13 (d, J=1.96 Hz, 1H) 9.16 (d, J=2.20 Hz, 1H) 10.69 (s, 1H).

Workup

  1. customThe solvent was evaporated off under reduced pressure
  2. additionthe residue was treated with water
  3. extractionextracted with EtOAc
  4. washThe combined extracts were washed with water and brine
  5. dry with materialdried over Na2SO4
  6. customthe solvent was evaporated off under reduced pressure
  7. customThe residue was purified by flash chromatography (Silica gel column, 500 g, EtOAc/MeOH from 0 to 2% MeOH)
  8. additionFractions containing the pure product
  9. customthe solvent was evaporated off under reduced pressure
  10. customto give a residue which
  11. filtrationfiltered
  12. customthe filtrate was evaporated off under reduced pressure

Sources & evidence

ORD record
ord-c779a821dbf745348fdaa2a8ca9cc95a
Source dataset
uspto-grants-2016_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09315489B2

Reaction notes

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