Dimethylformamide → HCID 178424031, compound

HRID 2173992Notes

Reaction equation

HRID 2173992 reaction equation
Br[C:2]1[CH:22]=[C:21]([F:23])[C:5]2[NH:6][C:7]([CH2:9][C:10]3[C:18]([CH3:19])=[CH:17][C:16]([CH3:20])=[C:15]4[C:11]=3[CH:12]=[CH:13][NH:14]4)=[N:8][C:4]=2[CH:3]=1.[CH3:24][N:25](C=O)C>CCOC(C)=O.[C-]#N.[Zn+2].[C-]#N.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.[Zn].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.[Fe+2].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:19][C:18]1[C:10]([CH2:9][C:7]2[NH:6][C:5]3[C:21]([F:23])=[CH:22][C:2]([C:24]#[N:25])=[CH:3][C:4]=3[N:8]=2)=[C:11]2[C:15](=[C:16]([CH3:20])[CH:17]=1)[NH:14][CH:13]=[CH:12]2

Participants

9

Reactant 2

HCID 6228DimethylformamideHCID 178424029HCID 178424029, compound

Product 1

HCID 178424031HCID 178424031, compound

Reagents, catalysts & solvents 6

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

Zinc cyanide (44 mg, 0.375 mmol) was weighed into a 50 mL flask, a degassed solution of 5-bromo-2-((5,7-dimethyl-1H-indol-4-yl)methyl)-7-fluoro-1H-benzo[d]imidazole (45 mg, 0.121 mmol) in DMF (4 mL) was added followed by Pd(Ph3P)4 (14 mg, 0.012 mmol). The reaction mixture was heated at 120° C. for 2 hours. Additional portions of zinc dust, dppf, and Pd2(dba)3 were added followed by heating to 130° C. until no starting material remained by LC-MS. The reaction was diluted with EtOAc and a saturated solution of NaHCO3, then filtered through a Celite® pad. The filtrate was extracted with EtOAc. The combined organic layers were dried over Na2SO4, filtered and concentrated to dryness. The residue was purified by reverse phase HPLC (HC-B) to afford the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.98 (br. s., 1H) 7.78 (s, 1H) 7.52-7.67 (m, 1H) 7.48 (d, J=10.61 Hz, 1H) 7.24 (t, J=2.78 Hz, 1H) 6.76 (s, 1H) 6.46 (dd, J=3.03, 2.02 Hz, 1H) 4.44 (s, 2H) 2.41 (s, 3H) 2.36 (s, 3H). HRMS calculated for C19H15FN4(M+H)+ 319.1354. found 319.1361.

Workup

  1. temperatureby heating to 130° C. until no starting material
  2. filtrationa saturated solution of NaHCO3, then filtered through a Celite® pad
  3. extractionThe filtrate was extracted with EtOAc
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe residue was purified by reverse phase HPLC (HC-B)

Sources & evidence

ORD record
ord-23d59da9c0d24459bddece27a39fef9f
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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