Hydrochloric Acid → HCID 66995423, compound

HRID 562926Notes

Reaction equation

HRID 562926 reaction equation
N1C(=O)C2NC=NC=2NC1=O.N1C=C2C(N=CN2)=NC=1.[OH-].[Na+].[NH2:23][C:24]1[CH:25]=[C:26]([C:30]2[CH:35]=[CH:34][C:33]([C:36]3[S:40][C:39]([C:41]([O:43]C)=[O:42])=[CH:38][CH:37]=3)=[CH:32][C:31]=2[C:45]#[N:46])[CH:27]=[CH:28][CH:29]=1.Cl>O1CCCC1.CO>[NH2:23][C:24]1[CH:25]=[C:26]([C:30]2[CH:35]=[CH:34][C:33]([C:36]3[S:40][C:39]([C:41]([OH:43])=[O:42])=[CH:38][CH:37]=3)=[CH:32][C:31]=2[C:45]#[N:46])[CH:27]=[CH:28][CH:29]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66995115HCID 66995115, compoundHCID 67533769HCID 67533769, compound

Product 1

HCID 66995423HCID 66995423, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A toluene (0.5 ml) suspension of 20 mg of methyl 5-(3-cyano-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)thiophene-2-carboxylate and 10 mg of potassium carbonate was added to 15 mg of 3-aminobenzeneboronic acid monohydrate, and in an argon atmosphere, 8 mg of tetrakis(triphenylphosphine)palladium was added thereto. The mixture was stirred overnight at 100° C., then cooled to room temperature, and filtered through Celite. The solvent was evaporated under reduced pressure to obtain methyl 5-(3′-amino-2-cyanobiphenyl-4-yl)thiophene-2-carboxylate. (2) 0.2 ml of aqueous 1 M sodium hydroxide solution was added to a methanol (0.25 ml)/tetrahydrofuran (0.25 ml) solution of methyl 5-(3′-amino-2-cyanobiphenyl-4-yl)thiophene-2-carboxylate, followed by stirring overnight at 60° C. 1 M hydrochloric acid was added to the reaction liquid to make it acidic, and the solvent was evaporated under reduced pressure. The residue was purified by HPLC [elution through column: SunFire (registered trademark) C18 5 μm, 19 mm×100 mm, solvent: MeOH/aqueous 0.1% formic acid solution=10/90 for 1 minute, ratio change to 95/5, taking 8 minutes, and further elution with 95/5 for 3 minutes, flow rate: 25 mL/min), thereby obtaining 2.5 mg of 5-(3′-amino-2-cyanobiphenyl-4-yl)thiophene-2-carboxylic acid.

Workup

  1. customthe solvent was evaporated under reduced pressure
  2. customThe residue was purified by HPLC [
  3. washelution through column
  4. waitSunFire (registered trademark) C18 5 μm, 19 mm×100 mm, solvent: MeOH/aqueous 0.1% formic acid solution=10/90 for 1 minute
  5. waitratio change to 95/5, taking 8 minutes
  6. washfurther elution with 95/5 for 3 minutes

Sources & evidence

ORD record
ord-c77843fd80604d6fac511a7928f05288
Source dataset
uspto-grants-2011_11
Patent number
US08067446B2

Reaction notes

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