Dimethylformamide → HCID 54612773, compound

HRID 573372Notes

Reaction equation

HRID 573372 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[N:17]=[CH:16][CH:15]=[CH:14][C:10]=2[C:11]([OH:13])=O)=[CH:4][CH:3]=1.CN(C=O)C.C(N=C=NCCCN(C)C)C.[NH2:34][C:35]1[S:36][C:37]2[CH:43]=[C:42]([F:44])[CH:41]=[CH:40][C:38]=2[N:39]=1>>[F:44][C:42]1[CH:41]=[CH:40][C:38]2[N:39]=[C:35]([NH:34][C:11](=[O:13])[C:10]3[CH:14]=[CH:15][CH:16]=[N:17][C:9]=3[NH:8][C:5]3[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=3)[S:36][C:37]=2[CH:43]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 3199542-Amino-6-fluorobenzothiazoleHCID 14325782-(4-Chloro-phenylamino)-nicotinic acid

Product 1

HCID 54612773HCID 54612773, compound

Conditions

Temperature
27 °C

Procedure

Compound 13 (185 mg, 1 mmol) and, 4-chloro aniline (17, 128 mg, 1 mmol) was taken in ethylene glycol and refluxed at 160° 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-chloro anilino) nicotinate (24) as pure product. Ethyl 2-(4-chloro anilino) nicotinate (24, 276 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-chlorophenylamino)nicotinic acid (31). To a stirred solution of 2-(4-chlorophenylamino) nicotinic acid (31, 249 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-fluoro benzothiazole (36, 118 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 (9) was purified by column chromatography employing EtOAc/Hexane as an eluent.

Workup

  1. customthe reaction mixture was quenched with NaHCO3
  2. extractionextracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer
  3. dry with materialdried over anhydrous Na2SO4
  4. customThe resulting product (9) was purified by column chromatography

Sources & evidence

ORD record
ord-d94df80095084765a141240f51584eba
Source dataset
uspto-grants-2015_05
Patent number
US09029553B2

Reaction notes

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