1,2-Dichloroethane → HCID 178509909, compound

HRID 1875082Notes

Reaction equation

HRID 1875082 reaction equation
C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[NH2:15][CH2:16][C:17]1[C:18]([F:34])=[C:19]([O:24][C:25]2[CH:26]=[C:27]([CH:30]=[C:31]([Cl:33])[CH:32]=2)[C:28]#[N:29])[C:20]([Br:23])=[CH:21][CH:22]=1.CC(OC([N:42](C(OC(C)(C)C)=O)[C:43]1[NH:44][C:45]([C:49](O)=[O:50])=[C:46]([Cl:48])[N:47]=1)=O)(C)C.[F:59][C:60]([F:65])([F:64])[C:61]([OH:63])=[O:62]>CN(C=O)C.ClCCl>[F:59][C:60]([F:65])([F:64])[C:61]([OH:63])=[O:62].[NH2:42][C:43]1[NH:44][C:45]([C:49]([NH:15][CH2:16][C:17]2[CH:22]=[CH:21][C:20]([Br:23])=[C:19]([O:24][C:25]3[CH:26]=[C:27]([C:28]#[N:29])[CH:30]=[C:31]([Cl:33])[CH:32]=3)[C:18]=2[F:34])=[O:50])=[C:46]([Cl:48])[N:47]=1

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 757711-HydroxybenzotriazoleHCID 671971663-{[3-(Aminomethyl)-6-bromo-2-fluorophenyl]oxy}-5-chlorobenzonitrileHCID 178454348HCID 178454348, compound

Product 1

HCID 178509909HCID 178509909, compoundYield 18%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

EDC (0.029 g, 0.152 mmol) and HOBT (0.021 g, 0.152 mmol) were added to a solution of 3-{[3-(aminomethyl)-6-bromo-2-fluorophenyl]oxy}-5-chlorobenzonitrile (0.049 g, 0.138 mmol) and 2-(bis{[(1,1-dimethylethyl)oxy]carbonyl}amino)-4-chloro-1H-imidazole-5-carboxylic acid (0.050 g, 0.138 mmol) in DMF (2 mL). The mixture was stirred at RT for 1 hr. The reaction mixture was extracted with EtOAc and saturated sodium bicarbonate. The organic layer was dried over sodium sulfate and concentrated to an oil. Dichloromethane (2 mL) and trifluoroacetic acid (0.5 mL, 6.49 mmol) were added and the mixture was stirred at RT overnight. The solvent was evaporated and the residue was purified by reverse phase HPLC (acetonitrile:water with 0.1% formic acid) to give the title compound (0.0103 g, 18%). 1H NMR (400 MHz, DMSO-d6) δ ppm 11.05 (br. s., 1H), 7.75-7.85 (m, 2H), 7.61 (d, 1H), 7.49 (s, 1H), 7.43 (m, 1H), 7.21-7.32 (m, 1H), 5.82 (br. s., 2H), 4.47 (d, 2H). LCMS: m/z 499 (M+1).

Workup

  1. extractionThe reaction mixture was extracted with EtOAc and saturated sodium bicarbonate
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated to an oil
  4. stirringthe mixture was stirred at RT overnight
  5. customThe solvent was evaporated
  6. customthe residue was purified by reverse phase HPLC (acetonitrile:water with 0.1% formic acid)

Sources & evidence

ORD record
ord-8d0452a4307040c1ae1a1d58b0c1340e
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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