Hydrochloric Acid → HCID 57394068, compound

HRID 573370Notes

Reaction equation

HRID 573370 reaction equation
[OH-].[Na+].Cl.[F:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11][C:12]2[N:20]=[CH:19][CH:18]=[CH:17][C:13]=2[C:14]([OH:16])=O)=[CH:7][CH:6]=1.CN(C=O)C.C(N=C=NCCCN(C)C)C.[NH2:37][C:38]1[S:39][C:40]2[CH:46]=[C:45]([N+:47]([O-:49])=[O:48])[CH:44]=[CH:43][C:41]=2[N:42]=1>C(O)C>[N+:47]([C:45]1[CH:44]=[CH:43][C:41]2[N:42]=[C:38]([NH:37][C:14](=[O:16])[C:13]3[CH:17]=[CH:18][CH:19]=[N:20][C:12]=3[NH:11][C:8]3[CH:7]=[CH:6][C:5]([F:4])=[CH:10][CH:9]=3)[S:39][C:40]=2[CH:46]=1)([O-:49])=[O:48]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 227042-Amino-6-nitrobenzothiazoleHCID 14222046HCID 14222046, compound

Product 1

HCID 57394068HCID 57394068, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
27 °C

Procedure

Compound 13 (185 mg, 1 mmol) and 4-fluoro aniline (16, 147 mg, 1 mmol) was taken in ethylene glycol and refluxed at 150° C. for 5 h. Then the reaction mixture was cooled and extracted in ethyl acetate (4×25 mL) from the aqueous layer and concentrated in vacuo. The compound was further purified by column chromatography using 60-120 silica gel (ethyl acetate/hexane, 1:9) to obtain Ethyl 2-(4-fluoroanilino) nicotinate (23) as pure product. Ethyl 2-(4-fluoroanilino) nicotinate (23, 260 mg, 1 mmol) were refluxed with 2N NaOH in ethanol for 2 h. The reaction mixture was cooled and left acidified with 2N HCl white solids obtained, filtered and washed with water to give pure compound of 2-(4-fluoroanilino)nicotic acid (30). To a stirred solution of 2-(4-fluorophenylamino) nicotinic acid (30, 232 mg 1 mmol) in dry DMF (10 mL) hydroxy benzotriazole HOBt (1.2 mmol) were added at 0° C. After 10 min 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDCI) (1.2 mmol) was added and finally 2-amino 6-nitro benzothiazole 37 (137 mg, 0.7 mmol) were added, then the resulting mixture was stirred at room temperature (27° C.) for 8-10 h and then the reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4. The resulting product (6) was purified by column chromatography employing EtOAc/Hexane as an eluent.

Workup

  1. temperatureThe reaction mixture was cooled
  2. waitleft
  3. customobtained
  4. filtrationfiltered
  5. washwashed with water
  6. customto give pure compound of 2-(4-fluoroanilino)nicotic acid (30)
  7. customthe reaction mixture was quenched with NaHCO3
  8. extractionextracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer
  9. dry with materialdried over anhydrous Na2SO4
  10. customThe resulting product (6) was purified by column chromatography

Sources & evidence

ORD record
ord-4965929e18974dff9d9ec14537521269
Source dataset
uspto-grants-2015_05
Patent number
US09029553B2

Reaction notes

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