Hydrochloric Acid → HCID 178510923, compound

HRID 2289989Notes

Reaction equation

HRID 2289989 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[CH:13]=[N:14][C:15]3[C:20]([C:21]=2[OH:22])=[CH:19][C:18](I)=[CH:17][C:16]=3[F:24])=[O:11])=[CH:4][CH:3]=1.CC1C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.[C:47](#[N:50])[CH:48]=[CH2:49].Cl>CC([O-])=O.CC([O-])=O.[Pd+2].CN(C=O)C.CCN(CC)CC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[CH:13]=[N:14][C:15]3[C:20]([C:21]=2[OH:22])=[CH:19][C:18](/[CH:49]=[CH:48]/[C:47]#[N:50])=[CH:17][C:16]=3[F:24])=[O:11])=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 7855AcrylonitrileHCID 80271Tri-o-tolylphosphineHCID 178522917HCID 178522917, compound

Product 1

HCID 178510923HCID 178510923, compoundYield 74%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Conditions

Temperature
100 °C

Procedure

A sealed tube was charged with N-(4-chlorobenzyl)-8-fluoro-4-hydroxy-6-iodo-3-quinolinecarboxamide from Example 5 (0.76 g), Pd(OAc)2 (0.0070 g), P(o-tolyl)3 (0.033 g), acrylonitrile (0.14 mL), NEt3 (0.59 mL), and DMF (4 mL). The tube was capped tightly and heated at 100° C. overnight behind a blast shield. The reaction was cooled to room temperature and poured into 20 mL 1N HCl. The resulting solid was filtered, dissolved in hot EtOH, and adsorbed onto silica. Chromatography on a Biotage Flash 40S column (eluent 1.5% MeOH:CH2Cl2 (2 L) followed by 2.5% MeOH:CH2Cl2 (1 L) and 3% MeOH:CH2Cl2 (1 L)) afforded the desired product as a tan solid (0.47 g, 74%).

Workup

  1. customThe tube was capped tightly
  2. temperatureThe reaction was cooled to room temperature
  3. filtrationThe resulting solid was filtered
  4. dissolutiondissolved in hot EtOH

Sources & evidence

ORD record
ord-248cccae84ff42aa9379333d951202a1
Source dataset
uspto-grants-2000_07
Patent number
US06093732

Reaction notes

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